Helminth Infections:
I.
Types a.
Aschelminths i.
Nematodes (roundworms) b.
Platyhelminths i.
Cestode and Trematode ii.
Flat worms
II.
Nematode infections: a.
Ancylostomiasis (Hookworms) – infections caused by the American hook worm (Nector americanus) or Oldworld hookworm (Ancylostoma
deoudenale) i.
Feed on human blood and tissue
1.
Suck energy ii.
Enters through the skin and travels to the lungs where it is coughed up and swallowed b.
Enterobiasis (Pinworms) – infections caused by Enterobius vermicularis i.
Female lays eggs in the perianal regions at night c.
Ascariasis (Roundworms) – infections caused by Ascaris lumbricoides i.
Eggs are found in the soils from which they are digested, travel to the lung and are swallowed to the GI d.
Trichuriasis (Whipworms) – infections caused by Trichuris trichiua i.
Embedded in wall of the intestine e.
Trichinosis – infections caused by Trichinella spiralis i.
Gets into the muscle tissue as well (extra-intestinal)
III.
Cestode and Trematode infections a.
Cysticercosis – Tapeworms b.
Schistosomiasis – blood flukes (Trematode infection) – infections caused by Schistosoma hematobium, S. mansoni and S. japonicum i.
From snails
IV.
Drug Therapy a.
Benzimidazole i.
Available drugs include Thiabendazole (Mintezole), Mebendazol
(Vermox) and Albendazole ii.
MOA:
1.
Inhibit fumarate reductase which converts NADH to NAD
2.
causes and uncoupling of oxidative phosphoralation
3.
decreases glucose transport
4.
***Inhibits microtubual formation a.
tubulin self associates into microtubules (?Backwards) b.
important for mitosis

c.
drug binds to the tubulin and prevents the microtubule formation and may even convert microtubulin back to tubulin iii.
Kinetics:
1.
low water solubility
2.
PO
3.
bound to plasma protein
4.
extensive metabolism a.
may account for biological activity iv.
Therapy:
1.
pregnancy category C
2.
used against a variety of internal helminthes
3.
has many complicating side effects a.
Thiabendazole: nausea/vomiting, anorexia, CNS effects, hepatic toxicities and SJS v.
Metabolism:
1.
Thiabendazole: undergoes aromatic hydroxylation and then conjugation with glucuronide or a sulfate a.
leaves and asparagus smell in the urine
2.
Mebendazole: undergoes either reduction of it’s ketone
(inactive) and then conjugation or hydrolysis of it’s side chain and conjugation a.
Conjugation is usually with glucuronides
3.
Albendazole: a.
Parent drug may be active b.
Converted via sulfer oxidation to its active compound and then to an inactive sulfone b.
Diethylcarbamazine (DEC, Hetrazan) i.
Piperizine derivative ii.
Has a tert. amine iii.
MOA: unknown
1.
does not work in vitro
2.
works in vivo (quickly) a.
too quickly for it to be a prodrug iv.
Available as a citrate salt
1.
forms at the lowest N (not neutral) v.
Metabolism:
1.
dealkylation on the upper amide
2.
N-oxidation on the middle N a.
Probably not responsible for activity vi.
Therapeutics:
1.
used against microflarial infections vii.
Side effects:

1.
anaphylactic reaction a.
immune response
2.
Mazzotti reaction a.
More prominent in people with a high load of worms c.
Avermectin and Ivermectin i.
Only difference between compounds is that Avermectin has a double bond between C22 and C23 ii.
MOA: paralysis of the muscle of the worm
1.
hyperpolarization of the membrane by inducing Cl influx iii.
Therapeutics:
1.
African river blindness (onchocerciasis)
2.
dosed q6mo or q1yr d.
Praziquantel (Biltricide) i.
Neutral molecule ii.
MOA: depends on use
1.
intestinal: paralysis of worm
2.
intravascular: effects tegament of worm a.
so body recognizes as foreign and attacks iii.
Therapeutics:
1.
schistomiasis and liver flukes a.
no activity against nematodes b.
can live 10 yrs and lay 300 eggs /day iv.
Metabolism:
1.
hydroxylated derivates (2 or 3) which are inactive a.
human metabolism e.
Pyrantel (Antiminth) i.
Available as a pamoate salt
1.
insoluble so that it stays in the intestinal tract with the worm ii.
Therapeutics:
1.
intestinal helminthes, enterobiasis (pinworm) iii.
MOA:
1.
neuromuscular blocking agent a.
cholinesterase blocking b.
leads to paralysis