2 - Systemic Antiparasitic Agents

Question 1

Ivermectin is a semisynthetic antihelminthic derived from fermentation products of Streptomyces avermitilis

Answer 1

True

Question 2

Ivermectin has structural similarity to that of macrolide antibacterial agents (erythromycin, clarithromycin, azithromycin)

Answer 2

True

Question 3

Although topical permethrin appears to be the most effective treatment for scabies, ivermectin appears to be an effective oral agent

Answer 3

True (data considering both cost and efficacy suggests that benzyl benzoate and ivermectin are most cost-effective for the treatment of scabies)

Question 4

In patients with crusted scabies, the response to oral ivermectin is variable and oral therapy in combination with topical scabicides and keratolytics are advocated

Answer 4

True (ivermectin alone often fails in crusted scabies)

Question 5

Ivermectin appears comparable or slightly inferior to permethrin in efficacy against non-crusted scabies, but has the convenience of oral dosing

Answer 5

True (ivermectin alone fails in crusted scabies)

Question 6

Ivermectin is primarily metabolised by CYP3A4 in the liver and excreted in the faeces

Answer 6

True (ivermectin is a substrate of CYP3A4)

Question 7

As <1% of the administered ivermectin dose is excreted in the urine (mainly faecal excretion), dose adjustment is needed with biliary obstruction but renal failure is not likely to affect metabolism

Answer 7

True (metabolised by the liver and excreted in the faeces)

Question 8

Bioavailability of ivermectin is increased when the drug is administered with a high-fat meal

Answer 8

True

Question 9

Ivermectin selectively binds to glutamate-gated chloride ion channels found in invertebrate (parasites) nerve and muscle cells, resulting in increased permeability of cell membranes to chloride ions and hyperpolarisation of the nerve/muscle cell causing death of the parasite

Answer 9

True

Question 10

Ivermectin is FDA approved in the treatment of intestinal strongyloides specifically caused by Strongyloides stercoralis, and onchocerciasis (river blindness) caused by Onchocerca volvulus

Answer 10

True (scabies is not FDA approved)

Question 11

Ivermectin is most widely used in dermatology (off label) for the treatment of scabies

Answer 11

True (200 ug/kg as a single dose, then repeated in 7-10 days) - addition of topical keratolytics and topical permethrin in crusted scabies

Question 12

Ivermectin is used in dermatology (off label) to some extent for the treatment of pediculosis (lice)

Answer 12

True (400 ug/kg as a single dose on Day 1 and Day 8)

Question 13

Ivermectin is used in dermatology (off label) to some extent for the treatment of cutaneous larva migrans

Answer 13

True

Question 14

A single dose of Ivermectin has also been used empirically (off label) to reduce the pruritus in homeless populations

Answer 14

True

Question 15

Ivermectin has been used in the control of hospital and institutional outbreaks of scabies, and may be superior to topical treatment in the setting of mass infestation

Answer 15

True

Question 16

Ivermectin is commonly associated with Mazzoti-type reactions (oedema, urticarial rash, systemic symptoms and ophthalmological reactions) when used in the treatment of helminthic infestations

Answer 16

True (less common in the setting of scabies)
NB. Mazzoti reactions may be due to allergic and inflammatory responses to the death of microfilariae or to microorganisms within the worms

Question 17

Ivermectin is commonly associated with pruritus in the setting on helminthic infestation

Answer 17

True (less common in the setting of scabies)

Question 18

Ivermectin is commonly associated with fever in the setting of helminthic infestation

Answer 18

True (less common in the setting of scabies)

Question 19

Ivermectin is commonly associated with lymphadenopathy or lymph node tenderness in the setting of helminthic infestation

Answer 19

True (less common in the setting of scabies)

Question 20

Tachycardia is an infrequent adverse reaction to Ivermectin

Answer 20

True

Question 21

The Mazzoti reactions commonly associated with ivermectin in patients with onchocerciasis may be due to allergic and inflammatory responses to the death of microfilariae or to microorganisms within the worms

Answer 21

True (doxycycline can eliminate endosymbiotic bacteria within filarial worms, and reducing the incidence of Mazzoti reactions)

Question 22

Doxycycline can eliminate endosymbiotic bacteria within filarial worms, and reducing the incidence of Mazzoti reactions in patients with onchocerciasis associated with ivermectin treatment

Answer 22

True

Question 23

Facial oedema is an infrequent adverse reaction to Ivermectin

Answer 23

True

Question 24

Orthostatic hypotension is an infrequent adverse reaction to Ivermectin

Answer 24

True

Question 25

Diarrhoea is an infrequent adverse reaction to Ivermectin

Answer 25

True

Question 26

Nausea is an infrequent adverse reaction to Ivermectin

Answer 26

True

Question 27

CNS symptoms is a rare adverse reaction to Ivermectin

Answer 27

True

Question 28

SJS is a rare adverse reaction to Ivermectin

Answer 28

True

Question 29

Abnormal LFTs is a rare adverse reaction to Ivermectin

Answer 29

True

Question 30

Ivermectin may enhance the anticoagulant effect of warfarin

Answer 30

True

Question 31

Australia has shown increasing increasing resistance to both topical permethrin and oral ivermectin in the treatment of scabies due to increased drug metabolism and efflux mechanisms

Answer 31

True

Question 32

Ivermectin is classified as pregnancy category C and teratogenic effects have been observed in animal studies

Answer 32

True

Question 33

Ivermectin is not recommended during lactation

Answer 33

True (enters breast milk, and safety and efficacy for use in children <15kg have not been established)

Question 34

Ivermectin is not recommended for children under 15kg

Answer 34

True

Question 35

Mass infestations of scabies are the best setting for the use of ivermectin

Answer 35

True

Question 36

Albendazole has both antihelminthic and antiprotozoal activity

Answer 36

True

Question 37

Albendazole has low aqueous solubility and so is poorly absorbed from the GI tract

Answer 37

True (oral bioavailability is enhanced when Albendazole is taken with a fatty meal)

Question 38

The systemic antihelminthic activity of Albendazole is attributed to its primary metabolite Albendazole sulfoxide

Answer 38

True (Albendazole is rapidly converted to the sulfoxide metabolite before reaching the systemic circulation, such that the plasma levels of Albendazole as the parent drug is negligible in plasma)

Question 39

Biliary elimination is the major route of excretion for Albendazole and its metabolite Albendazole sulfoxide, with <1% excreted in the urine

Answer 39

True (biliary obstruction will affect blood levels, but renal failure is unlikely to affect levels)

Question 40

Albendazole sulfoxide (major metabolite of Albendazole) is mainly bound to plasma protein and achieves excellent distribution throughout the body

Answer 40

True

Question 41

Albendazole inhibits tubulin polymerisation, which causes immobilisation and death of the susceptible organisms

Answer 41

True

Question 42

Albendazole is FDA approved for the treatment of neurocystocercosis and hydatid disease (tapeworms)

Answer 42

True

Question 43

Ivermectin is significantly more effective than Albendazole for pediculosis

Answer 43

True

Question 44

Albendazole has not been adequately studied in children under 1 year of age

Answer 44

True

Question 45

Albendazole may cause bone marrow suppression with aplastic anaemia and agranulocytosis

Answer 45

True

Question 46

Bone toxicity may occur in patients on Albendazole with and without underlying hepatic dysfunction and FBC should be monitored

Answer 46

True (biliary obstruction affects blood levels as the drug is mainly excreted in the bile)

Question 47

Patients with liver disease on Albendazole appear to be at an increased risk for bone marrow suppression

Answer 47

True (biliary obstruction affects blood levels as the drug is mainly excreted in the bile)

Question 48

Other adverse effects of Albendazole include hepatotoxicity

Answer 48

True

Question 49

Other adverse effects of Albendazole include GI discomfort

Answer 49

True

Question 50

Other adverse effects of Albendazole include diarrhoea

Answer 50

True

Question 51

Other adverse effects of Albendazole include headache

Answer 51

True

Question 52

Other adverse effects of Albendazole include dizziness

Answer 52

True

Question 53

Hypersensitivity reactions presenting with rash, pruritus or urticaria is rarely associated with Albendazole

Answer 53

True

Question 54

Albendazole is a CYP1A2 inhibitor

Answer 54

True (may inhibit theophylline metabolism as theophylline is a CYP1A2 substrate)

Question 55

Albendazole is classified as pregnancy category C as it is both teratogenic and embryotoxic in animal studies

Answer 55

True (pregnancy test should be obtained before starting therapy)

Question 56

Thiabendazole is a broad spectrum antihelminthic that has been used for the treatment of parasitic infestations in humans and animals

Answer 56

True

Question 57

Thiabendazole is metabolised almost entirely by the liver and the metabolites are substantially excreted by the kidneys

Answer 57

True (therefore the drug should be used with caution and the dose may need to be adjusted in patients with impaired hepatic or renal function)

Question 58

Thiabendazole is rapidly absorbed and metabolised almost completely to its 5-hydroxy form in the liver

Answer 58

True

Question 59

The mechanism of action of thiabendazole is unknown but it may inhibit the helminth-specific fumarate reductase

Answer 59

True

Question 60

Thiabendazole is indicated for the treatment of strongyloidiasis

Answer 60

True

Question 61

Thiabendazole is indicated for the treatment of cutaneous larva migrans

Answer 61

True

Question 62

Thiabendazole is indicated for the treatment of visceral larva migrans

Answer 62

True

Question 63

Thiabendazole has been used for the treatment of intestinal roundworms infestation

Answer 63

True

Question 64

Thiabendazole has been associated with hepatotoxicity

Answer 64

True

Question 65

Thiabendazole has been associated with anorexia and abdominal symptoms such as nausea, vomiting, diarrhoea, and abdominal pain

Answer 65

True

Question 66

Thiabendazole has been associated with CNS symptoms such as convulsions, confusion, tinnitus and depression

Answer 66

True

Question 67

Thiabendazole has been associated with SJS

Answer 67

True

Question 68

Thiabendazole is a CYP1A2 inhibitor

Answer 68

True (may increase theophylline and caffeine levels as these 2 are CYP1A2 substrates)

Question 69

Thiabendazole is classified as pregnancy category C as birth defects have been observed in animal studies

Answer 69

True

Question 70

Ivermectin may rarely cause potentially fatal encephalopathy in patients co-infected with loiasis

Answer 70

True