Title: Anthelmintics SCHISTOSOMIASIS
1Anthelmintics SCHISTOSOMIASIS
Alia Alshanawani Pharmacology Dep, Medical
College KSU.
2 - TREMATODES
- also called as flukes
- are leaf shaped flat worms
- characterized by ! tissues they infect as
parasite - Lung / Liver / Intestinal / Blood FLUKES.
3 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.
4- 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.
5LIFE CYCLE
6 - 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.
7 - 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.
8 Antischistosomal drugs
- Praziquantel (all schistosomal diseases)
- 2. Metrifonate (S. haematobium)
- 3. Oxamniquine (S. mansoni).
-
9 - 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.
10 - 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).
11- Mechanism of Action of praziquantel
-
- increases trematode cell membrane permeability to
Ca2 contraction, paralysis, dislodgement
death.
12- 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.
13- 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.
14- taken after meals.
- the interval between doses should not be lt than
4 hr not gt than 6 hr. - effective in children adults.
15- 2- Other trematodes infections
- Clonorchiasis (liver), paragonimiasis (lung)
- 3- Cestodes infections
- Taeniasis diphyllobothriasis (intestine)
- Neurocysticercosis (albendazole is preferred)
- Hymenolepis nana
- Hydatid disease.
16- 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.
17Adverse reactions of praziquantel
- In neurocysticercosis neurologic abnormalities
(headache, mental changes, seizures) increases by
inflammation around dying parasite. - Rx
- used with corticosteroids.
18Contraindication 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
19Metrifonate (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.
20Pharmacodynamics 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.
21Clinical 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.
22- 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.
23Contraindications cautions Metrifonate
- Pregnancy.
- Recent exposure to insecticides / drugs that
potentiate cholinesterase inhibition.
24Oxamniquine
- Semisynthetic tetra-hydro-quinoline
- PK
- po
- T1/2 2.5 hr
- extensively metabolize into inactive metabolites.
- excreted via kidney.
25Anthelmintic 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.
26USES of Oxamniquine
- Alternative to praziquantel for Tr of all stages
of S. mansoni ONLY. - Effective in praziquantel resistance.
27Clinical 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.
28Adverse reactions Oxamniquine
- CNS Dizziness , headache, drowsiness
- GIT disturbance
- Pruritus, urticaria, fever
- Discoloration of urine (orange-red)
- Proteinuria
- Transient elevation of liver enzymes
- Seizures.
29Contraindications Precautions Oxamniquine
- Epilepsy
- Pregnancy
- Activities require alertness.