Antihelminthics

Question 1

Benzimidazoles mechanism of action

Answer 1

Inhibit microtubule polymerization - much higher affinity for parasite tubulin over mammalian. This inhibits mitosis, secretion, and organelle movement.

Question 2

Benzimidizole Resistance

Answer 2

Changes in Beta tubulin isotype, point mutation in beta tubulin.

Question 3

Mebendazole ADME

Answer 3

Pharmacologically active, poorly absorbed. This allows it to be used for infections in the GI tract, but not for systemic infections.

Question 4

Albendazole ADME

Answer 4

Erratic absorbtion, helped by fatty food/bile salts. Rapid 1st pass activation - penetrates tissues and hyatid cysts. GI AND Systemic infections.

Question 5

Mebendazole toxicity

Answer 5

Transient abdominal distress in short term treatment. High dose therapy, bone marrow suppression, alopecia, elevated LFT’s. Rare seizures.

Question 6

Mebendazole contraindications

Answer 6

Pregnancy, Children under 2.

Question 7

Albendazole Toxicity

Answer 7

Short term - mild epigastric distress, HA, dizziness, NVD. Transiet LFT elevation. Longer term use bone marrow suppression, alopecia, elevated LFTs.

Question 8

Albendazole contraindications

Answer 8

Pregnancy, and safety in children under 2 is unknown.

Question 9

Ivermectin Mechanism

Answer 9

Activates an invertebrate specific glutamate gated chloride channel, leading to hyperpolarization and muscle paralysis.

Question 10

Ivermectin is effective against

Answer 10

Onchocerciasis, Lymphatic filiariasis (with Albendazole), Loaisis.

Question 11

Use of Ivermectin to treat Onchocerciasis

Answer 11

Administered every 6-12 months for 50-10 years. Used in combination with corticosteroids due to strong inflammatory response to dying worms that can cause tissue damage.

Question 12

Use of Ivermectin in lymphatic filariasis

Answer 12

Used in combo with albendazole, because it appears to be ineffective against adult worms.

Question 13

Ivermectin Effectiveness against Trematodes and Cestodes

Answer 13

NOT EFFECTIVE - they do not express the right kind of chloride channel.

Question 14

Ivermectin ADME

Answer 14

Readily absorbed, Plasma distributed. Half life 57 HOURS! CYP3A4 metabolism. Does not cross BBB.

Question 15

Ivermectin contraindications

Answer 15

Impaired blood brain barrier, Loa Loa (disability and encephalopathy)

Question 16

Ivermectin toxicity

Answer 16

Generally well tolerated, but watch out for the inflammatory response to dying worms. - Itchy lymphadenopathy, headache, dizziness, edema, etc.

Question 17

Praziquantel Mechanism of Action

Answer 17

Increase influx of calcium, causing paralysis, and allowing the host immune system access to more antigens.

Question 18

Praziquantel is effective against

Answer 18

Trematodes, cestodes (including shistosomiasis), Kills adult and immature worms.

Question 19

Praziquantel is NOT effective against

Answer 19

NEMATODES

Question 20

Praziquantel ADME

Answer 20

Readily absorbed, dose related half life. bioavailability reduced with steroids.

Question 21

Praziquantel toxicity

Answer 21

Abdominal pain, nausea, HA, dizziness, drowziness,

Question 22

Praziquantel and P450 -effecting drugs

Answer 22

CYP inhibitors increase bioavailability. CYP inducers decrease bioavailability .

Question 23

Praziquantel counterindications

Answer 23

pregnancy, Intraocular cystercosis (pork tapeworm) - surgery instead.

Adjust dose in liver failure

Question 24

Diethylcarbamazine is effective against

Answer 24

Loiasis, Lymphatic filariasis (with albendazole)

Question 25

Diethylcarbamazine contraindications

Answer 25

Onchocerciasis - SEVERE inflammation.

Question 26

Diethylcarbamazine mechanism

Answer 26

Unknown, does something to the worm surface membrane, stimulating platelet aggregation and immune response.

Question 27

Diethylcarbamazine ADME

Answer 27

Rapid absorbtion, Half life 2-10hrs depending on urine pH. Alkalize the urine to make it last longer. Excretion is renal.

Question 28

Diethylcarbamazine toxicity

Answer 28

Generally nothing to worry about, BUT there can be a major inflammatory reaction to antigenic proteins from dying worms. - use steroids to reduce.

Question 29

Pyrantel Pamoate is effective against

Answer 29

Nematodes - pinworm, ascaris, trichostronglylus orientalis.

Question 30

Pyrantel Pamoate mechanism

Answer 30

Depolarizing neuromuscular blocker at nicotinic receptors - release of Ach and block of Achesterase- spastic paralysis.

Question 31

Pyrantel Pamoate ADME

Answer 31

Poorly absorbed - effective in GI tract only, expelled in feces.

Question 32

Pyrantel Pamoate toxicity

Answer 32

Transient mild GI symptoms, HA, rash, fever. At high doses, it starts to affect the host’s nicotinic receptors, leading to neuromuscular blockade.