Anthelmintics SCHISTOSOMIASIS

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Anthelmintics SCHISTOSOMIASIS
Alia Alshanawani Pharmacology Dep, Medical
College KSU.
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• TREMATODES
• also called as flukes
• are leaf shaped flat worms
• characterized by ! tissues they infect as
  parasite
• Lung / Liver / Intestinal / Blood FLUKES.

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Schistosomiasis Also known as
bilharzia, bilharziosis / snail fever is a
parasitic disease caused by several species of
fluke of ! Genus Shistosomiasis. Caused by
trematodes 1. Schistosoma haematobium 2. S.
mansoni 3. S. japonicum.
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• Although it has a low mortality rate,
  schistosomiasis often is a chronic illness that
  can damage internal organs , in children, impair
  growth cognitive development.
• The urinary form of schistosomiasis is
  associated with increased risks for bladder
  cancer in adults.
• Schistosomiasis is the 2nd most
  socioeconomically devastating parasitic disease
  after malaria.

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LIFE CYCLE
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• Schistosomiasis (New world)
• S. mansoni S. Japonicum
• Primary site of infection is GIT.
• Damage to intestinal wall is caused by hosts
  inflammatory response to eggs deposited at that
  site.
• The eggs also secrete proteolytic enzymes that
  further damage ! tissue.
• Diagnosis eggs in stools.
• GIT bleeding, diarrhea, Liver damage.

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• Schistosomiasis (old world)
• S. Haematobium
• ! primary sites of infection veins of urinary
  bladder
• eggs induce fibrosis , granulomas haematuria.
• transmitted by direct skin penetration.
• Diagnosis eggs in ! urine / bladder wall.

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Antischistosomal drugs

• Praziquantel (all schistosomal diseases)
• 2. Metrifonate (S. haematobium)
• 3. Oxamniquine (S. mansoni).

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• Praziquantel
• a synthetic isoquinoline pyrazine derivative
• PK
• rapid po absorption
• maximum plasma conc 1-3 hr.
• Cross BBB.
• bound to plasma proteins (80).
• undergoes 1st pass metabolism to inactive
  metabolite.

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• T1/2 0.8 - 3 hr (increases in liver disease).
• excreted in urine bile.
• Bioavailability
• Increased by carbohydrate meal cimetidine.
• Reduced by antiepileptics (phenytoin
  carbamazepine).

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• Mechanism of Action of praziquantel
• increases trematode cell membrane permeability to
  Ca2 contraction, paralysis, dislodgement
  death.

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• Anthelminthic action praziquantel
• broad spectrum anthelminthic drug
• effective in the Tr of schistosome infections of
  all species most other trematodes cestodes
  (tapeworms) but
• nematodes (round worms) are unaffected.
• effective against mature immature stages of
  worms.
• Cure rate is up to 95.

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• Clinical uses praziquantel
• Schistosomiasis
• Drug of choice for all forms
• For S.Japonicum infections, 20 mg/kg at
  intervals 4-6 hours for a total of 3 doses.
• For S.mansoni and S.hamatobium 40 mg /kg in two
  divided doses.

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• taken after meals.
• the interval between doses should not be lt than
  4 hr not gt than 6 hr.
• effective in children adults.

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• 2- Other trematodes infections
• Clonorchiasis (liver), paragonimiasis (lung)
• 3- Cestodes infections
• Taeniasis diphyllobothriasis (intestine)
• Neurocysticercosis (albendazole is preferred)
• Hymenolepis nana
• Hydatid disease.

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• Adverse reactions of praziquantel
• Headache, dizziness, drowsiness.
• GIT disturbances.
• Pruritus, urticaria, arthralgia, myalgia.
• transient elevation of liver enz.
• Fever, skin rashes , augmented eosinophilia may
  appear after several days release of foreign
  protein from dying worm.

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Adverse reactions of praziquantel

• In neurocysticercosis neurologic abnormalities
  (headache, mental changes, seizures) increases by
  inflammation around dying parasite.
• Rx
• used with corticosteroids.

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Contraindication precautions

• Ocular cysticercosis for fear of destruction of
  parasite in eye.
• Children lt 4 years.
• Pregnancy nursing mothers.
• Driving.
• Activities require alertness physical
  coordination (prohibited).
• Reduce the dose in liver impairment.
• Patient should be informed not chewing bitter
  taste

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Metrifonate (TRICHLORFON)

• Organo-phosphate compound
• PK
• Rapid po absorption.
• t1/2 1.5 hr.
• Nonenzymatic transformed to active metabolite.
• widely distributed to tissues.
• Excreted in urine.

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Pharmacodynamics Metrifonate

• produces its effect due to inhibition of
  cholinesterase, produces depolarizing block of S.
  haematobium
• paralyzes the adult worm their shift from
  bladder venous plexus to a small arterioles of
  the lungs, where they are trapped by ! immune
  system killed.
• NOT effective against S. haematobium eggs, only
  adult worms are killed.

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Clinical uses Metrifonate

• Safe, low cost alternative drug for S. hematobium
  infections ONLY .
• A single dose of 7.5-10 mg /kg 3 times at 14 days
  intervals.
• effective as prophylactic when given monthly to
  children in a highly endemic area.
• In mixed infection with S. haematobium S.
  mansoni metrifonate oxamniquine.

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• Adverse reactions of Metrifonate
• Mild cholinergic symptoms
• N , V, diarrhea, abdominal pain,
• B.spasm, headache, sweating, fatigue, weakness,
  dizziness,
• vertigo
• these start after 30 min persist up to 12 hr.

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Contraindications cautions Metrifonate

• Pregnancy.
• Recent exposure to insecticides / drugs that
  potentiate cholinesterase inhibition.

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Oxamniquine

• Semisynthetic tetra-hydro-quinoline
• PK
• po
• T1/2 2.5 hr
• extensively metabolize into inactive metabolites.
• excreted via kidney.

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Anthelmintic actions

• Effective against mature immature stages of S.
  mansoni ONLY.
• Its mechanism of action is unknown.
• It may cause contraction paralysis of worms
  its detachment from the mesentery shift to the
  liver where worm may die.
• Surviving females may return to mesenteric
  vessels but cease to lay eggs.

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USES of Oxamniquine

• Alternative to praziquantel for Tr of all stages
  of S. mansoni ONLY.
• Effective in praziquantel resistance.

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Clinical uses

• Less effective in children (higher doses)
• better tolerated with food.
• 15 -20 mg /kg twice for 1 day.
• In mixed infection with S.H S.M metrifonate
  oxamniquine.

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Adverse reactions Oxamniquine

• CNS Dizziness , headache, drowsiness
• GIT disturbance
• Pruritus, urticaria, fever
• Discoloration of urine (orange-red)
• Proteinuria
• Transient elevation of liver enzymes
• Seizures.

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Contraindications Precautions Oxamniquine

• Epilepsy
• Pregnancy
• Activities require alertness.