2 - Topical and Intralesional Antiviral Agents

Question 1

Topical and intralesional agents can be:

(1) viricidal
(2) immune-enhancing
(3) cytodestructive

Answer 1

True

Question 2

The topical viricidal agents include:

(1) acyclovir
(2) penciclovir
(3) cidofovir
(4) foscarnet
(5) idoxuridine

Answer 2

True

Question 3

The topical/intralesional immune enhancers include:

(1) topical imiquimod
(2) topical and intralesional interferon

Answer 3

True

Question 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

Answer 4

True

Question 5

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

Answer 5

True

Question 6

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

Answer 6

True

Question 7

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

Answer 7

True

Question 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

Answer 8

True

Question 9

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

Answer 9

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

Question 10

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

Answer 10

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

Question 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

Answer 11

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

Question 12

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

Answer 12

True

Question 13

Both topical acyclovir and penciclovir are classified as pregnancy category B

Answer 13

True

Question 14

Topical cidofovir and foscarnet are classified as pregnancy category C

Answer 14

True (listed for the injectable version of the drug)

Question 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

Answer 15

True

Question 16

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

Answer 16

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

Question 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

Answer 17

True

Question 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

Answer 18

True

Question 19

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

Answer 19

True (limited activity against CMV)

Question 20

Penciclovir exhibits limited in vitro inhibitory activity against CMV

Answer 20

True

Question 21

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

Answer 21

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)

Question 22

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

Answer 22

True

Question 23

The most frequently reported adverse effect with topical Penciclovir is headache

Answer 23

True

Question 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

Answer 24

True

Question 25

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

Answer 25

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

Question 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

Answer 26

True

Question 27

IV Cidofovir is used to treat CMV retinitis in AIDS patients

Answer 27

True

Question 28

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

Answer 28

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

Question 29

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

Answer 29

True

Question 30

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

Answer 30

True

Question 31

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

Answer 31

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

Question 32

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

Answer 32

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

Question 33

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

Answer 33

True (reported anecdotally or in small studies)

Question 34

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

Answer 34

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

Question 35

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

Answer 35

True

Question 36

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

Answer 36

True

Question 37

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

Answer 37

True

Question 38

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

Answer 38

True

Question 39

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

Answer 39

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

Question 40

Foscarnet does not require activation by either cellular or viral enzymes

Answer 40

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

Question 41

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

Answer 41

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)

Question 42

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

Answer 42

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

Question 43

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

Answer 43

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

Question 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

Answer 44

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

Question 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

Answer 45

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

Question 46

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

Answer 46

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

Question 47

Imiquimod is a non-nucleoside heterocyclic amine

Answer 47

True

Question 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

Answer 48

True

Question 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

Answer 49

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)

Question 50

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

Answer 50

True

Question 51

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

Answer 51

True

Question 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

Answer 52

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

Question 53

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

Answer 53

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

Question 54

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

Answer 54

True

Question 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

Answer 55

True

Question 56

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

Answer 56

True | Overnight application 5X weekly

Question 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

Answer 57

True

Question 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

Answer 58

True

Question 59

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

Answer 59

True

Question 60

Imiquimod is undergoing trial for the treatment of lentigo maligna melanoma

Answer 60

True

Question 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

Answer 61

True

Question 62

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

Answer 62

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

Question 63

Bleomycin has antitumour activity

Answer 63

True

Question 64

Bleomycin has antibacterial activity

Answer 64

True

Question 65

Bleomycin has antiviral activity

Answer 65

True

Question 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

Answer 66

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

Question 67

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

Answer 67

True

Question 68

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

Answer 68

True

Question 69

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

Answer 69

True (not FDA approved)

Question 70

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

Answer 70

True

Question 71

Intralesional Bleomycin should not be used in pregnant women

Answer 71

True

Question 72

Intralesional Bleomycin should not be used in children

Answer 72

True

Question 73

Intralesional Bleomycin should not be used in immunosuppressed patients

Answer 73

True

Question 74

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

Answer 74

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

Question 75

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

Answer 75

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

Question 76

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

Answer 76

True

Question 77

Scarring is an uncommon adverse effect from Intralesional Bleomycin

Answer 77

True

Question 78

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

Answer 78

True

Question 79

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

Answer 79

True

Question 80

Persistent nail dystrophy is an uncommon adverse effect from Intralesional Bleomycin

Answer 80

True

Question 81

Flagellate hyperpigmentation is an uncommon adverse effect from Intralesional Bleomycin

Answer 81

True

Question 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

Answer 82

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

Question 83

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

Answer 83

True

Question 84

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

Answer 84

True

Question 85

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

Answer 85

True

Question 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

Answer 86

True

Question 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

Answer 87

True

Question 88

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

Answer 88

True

Question 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

Answer 89

True

Question 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

Answer 90

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

Question 91

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

Answer 91

True

Question 92

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

Answer 92

True

Question 93

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

Answer 93

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)

Question 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

Answer 94

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

Question 95

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

Answer 95

True

Question 96

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

Answer 96

True

Question 97

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

Answer 97

True

Question 98

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

Answer 98

True

Question 99

Cantharidin has no direct antiviral effect

Answer 99

True

Question 100

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

Answer 100

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

Question 101

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

Answer 101

True

Question 102

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

Answer 102

True

Question 103

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

Answer 103

True (less frequently also noted post cryotherapy)

Question 104

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

Answer 104

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

Question 105

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

Answer 105

True

Question 106

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

Answer 106

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

Question 107

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

Answer 107

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)

Question 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

Answer 108

True

Question 109

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

Answer 109

True

Question 110

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

Answer 110

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

Question 111

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

Answer 111

True

Question 112

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

Answer 112

True

Question 113

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

Answer 113

True

Question 114

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

Answer 114

True