Transcript Antihelminthic

HELMINTHIC
INFECTIONS
HELMINTHS
• Macroscopic,
multiceullar organism
• Having
their
own
digestive
system,
excretory, reproductive
and nervous systems
INTRODUCTION
GENERAL FEATURES
• Humans are the primary hosts.
• Most
worms
produce
in
• Worm-like parasites
human
sexually
• By producing eggs and larvae.
• These pass out of body and infect the
secondary host.
• Imature forms invade humans via
skin or GIT.
• Mature
to
adult
worms
characterstic tissue distribution.
with
• Outer
protective
cuticle/integument
covering-
• Locomotion-muscular contraction
& relaxation.
• Eggs or larvae produced
enormous numbers.
in
• Inability to multiply in the body
of the host.
CLASSIFICATION
• Based on external and internal morphology of egg,
larval, and adult stages & the host organ they
inhabit
1)NEMATHELMINTHES
-Cylindrical round worms
a) NEMATODES
Eg: ascaris, ancylostoma, trichuris, strongyloides, enterobius, filariasis, dracunculus.
2) PLATYHELMINTHES
-Flat worms
a) TREMATODES or Flukes :• Leaf-like.
Eg.Blood flukes(schistosomiasis), fasciola, clonorchis, paragonimus,
b) CESTODES or Tape worms:• Tape-like
Eg.Taenia,echinococcus,diphyllobothrium
NEMATELMINTHS(ROUND)
• ROUND WORMS
• ASCARIS.L
• HOOK WORMS
• NECATOR A
• WHIP WORMS
• TRICHURIS T
• THREAD WORMS
• STRONGYLOIDES.S
• PIN WORMS
• ENTEROBIUS V
• FILARIASIS WORMS
• BANCROFTI
• ONCHOCERCIASIS
• O.VOLVULUS
• GUINEA WORMS
• DRACANCULUS M
PLATYHELMINTHS
A) TREMATODES-FLUKES
• BLOOD FLUKES
• SCISTOSOMIASIS
• LIVER FLUKES
• CLONORCHIASIS
• INTESTINAL FLUKES
• FASCIOLOPSIASIS
• LUNG FLUKES
• PARAGONIMIASIS
B) CESTODES
• BEEF TW
• T.SAGINAT
• PORK TW
• T.SOLIUM
• FISH TW
• DIPHYLLOBO THRIUM
• DWARF TW
• HYMENOLEPIS.NANA
TYPES (CLINICAL)
1.
Worms live in hosts
alimentary canal.
2.
Worms
or
larvae
live in other tissues of
host body like muscles ,
viscera , menninges ,
lungs,
tissues.
subcutaneous
1)INTESTINAL
A) ROUND WORMS
(NEMATODES)
• Ascaris lmubricods (common round
worm)
• Enterobius vermicularis (pin worm)
• Trichuris trichuria ( whip worm)
• Strongyloids stercoralis (thread
worm)
• Ankylostoma
dudenale
(hook
worm)
B)
TAPE
(CESTODES)
•
•
•
•
WORMS
Taenia saginata(Beaf) ,
Taenia solium(Pork),
Hymenolepis nana(Dwarf) ,
Diphylobothrium latum(Fish)
2. TISSUE WORMS
A) TREMATODES (Schisotomes)
OR FLUKES(leaf like)
• Schistosoma haematobium
• Schistosoma Japonicum
• Schistosoma mansoni
(These cause SCHISTASOMIASIS ) also
called (BILHARZIA) means disease of
blood vessels.
• Clonorchis sinensis (liver fluke)
• Paragonimus westermani (lung fluke)
B) TISSUE ROUND WORMS
• Trichnella spiralis.
• Dracunulus medinensis (guinea
worm) larva
• FILARIAE includes
•
Wuchereria bancrofti
• Loa loa
• Onchocerera volvulus
• Brugia malayi
C) HYDATID TAPE WORM
NEMATHELMINTHS
• Long,
round
bodies,
unsegmented worms, tapered
at both ends.
• Most
found primarily in
intestine.
• Attached to the mucosa and
feed host blood and tissue
fluid.
Symptoms:Abdomianl pain
Diarrhoea
Pruritis
In severe condition cause
anaemia
PLATYHELMINTHS
A)Trematodes (Flukes)
• Non segmented
• Acquired - ingestion of food
• Mature in intestinal track
• Migrate and mature in liver- Liver
flukes
• Lung – Lung flukes
Causes:
• Diarrhoea
• Abdominal pain
• Anorexia
Liver flukes:
•
•
•
•
Bile duct obstruction
Liver enlargement
Cirrhosis of liver
Diarrhoea
Lung flukes:
• Cough
• Haemoptysis
Blood flukes:
Skin
Lung
Liver
Mature
Blood
• Haematuria
• Frequent & painful micturation
• Abdominal pain
•CESTODES:
• Ribbon shaped
• Intestinal parasites
• Head, neck followed
by segments
• Head hold- intestinal
walls
• No digestive system host nutrients
ROUND WORM
filariasis
Hookworm
Pin worm male, female
LIFE CYCLE OF HELMINTHS
• Adult worms live in the lumen of the small intestine.
• A female may produce approximately 200,000 eggs per day, which are
passed with the feces .
• Fertile eggs embryonate and become infective , depending on the
environmental conditions (optimum: moist, warm, shaded soil).
• After infective eggs are swallowed
• The larvae hatch
• Invade the intestinal mucosa portal, systemic circulation lungs 
penetrate the alveolar walls ascend the bronchial tree to the throat, and
are swallowed .
• Upon reaching the small intestine, they develop into adult worms.
• Between 2 and 3 months are required from ingestion of the infective eggs to
oviposition by the adult female.
• Adult worms can live 1 to 2 years.
ANTHELMINTICS OR
ANTIHELMINTHICS
• Drugs that expel parasitic worms (helminths) from the body by either
stunning or killing them.
• They may also be called vermifuges (stunning) or vermicides (killing).
CLASSIFICATION
• AGAINST NEMATODES
• ALBENDAZOLE, MEBENDAZOLE, PYRANTEL PAMOATE, LEVIMASOLE, PIPERAZINE, IVERMECTIN,
DIETHYLCARBAMAZINE, THIABENDAZOLE, DOXYCYCLINE
• AGAINST TREMATODES
• METRIFONATE, OXAMNIQUINE, BITHIONOL, TRICLABENDAZOLE
• AGAINST CESTODES
•
NICLOSAMIDE
• AGAINST TREMATODES AND CESTODES
•
PRAZIQUANTEL
MEBENDAZOLE
• A synthetic benzimidazole
• Introduced in 1972
• Broad-spectrum
SPECTRUM:
• 100% cure rate
• For round worm, hook worm, enterobius
(less for Strongyloides) and trichuris (not
for tissue Trichinella spiralis)
• 75% effective
• For tape worms but not for H. nana
• Hadatid cyst: prolonged treatment
• Hatching of nematode eggs and larva
inhibited and Ascaris eggs are killed
MECHANISM OF ACTION
• Action is slow: takes 2-3 days to
develop.
• Inhibits microtubule synthesis
• That irreversibly impairs glucose
uptake
• Inhibition of glucose uptake
• Disruption of metabolic pathway
• Resulting
in
the
gradual
immobilization and die slowly.
CLINICAL USES
•Pinworm
•Trichuriasis
•Hookworm
•Ascaris infections.
•Whipworm
•Enterobius
•Trichinella spiralis
•Hydatid disease
ADVERSE EFFECT
In heavy infestation
cases:• Diarrhoea
• Nausea
• Abdominal pain
In high dose:• Granulocytopenia
• Allergic reaction
• Alopecia
ALBENDAZOLE
MECHANISM OF ACTION
• Congener of Mebendazole
• Broad-spectrum activity
• Excellent tolerability
• Single dose administration
SPECTRUM OF ACTION
• Comparable efficacy
mebendazole
with
• Same for round worm, hook worm and
enterobius
• Less effective against trichuris
• More effective against strongyloides
• Trichinella effectiveness is almost same
• More effective in tape worm (including H.
nana) and hydatid larvae and ova of
ascaris and hook worm
• Weak microfilarial action and cutaneous
larva migrans
• Binds with β-tubulin and
inhibits
microtubules
polymerization.
• Blocks glucose and other
nutrients uptake.
• Intestinal
parasites
are
immobilized and die slowly.
PHARMACOKINETICS
• Benzimidazole carbamate
• Moderate and inconsistent oral
absorption
• Fatty meals enhance absorption
• For intesinal worm given in
empty stomach and for tissue
action – with fatty meals
ADVERSE EFFECT
• Well tolerated
• GI side effects
• Dizziness
• Prolonged used in
hydatid
and
cysticercosis
-
Headache,
fever,
alopecia, neutropenia,
jaundice.
USES
• Used on empty stomach when
used against intestinal worms
• With a fatty meal when used
against cysticercosis, hydatid and
cutaneous larva migrans .
• Ascaris, hookworm, Enterobius
and Trichuris
• Tapeworms and strongyloidosis
• Trichinosis
• Neurocysticercosis
• Cutaneous larva migrans
• Hydatid disease
• Filariasis
THIABENDAZOLE
• First benzimidazole polyanthelmintic
• Introduced in 1961
SPECTRUM
• All species of nematodes infesting
the g.i.t.-roundworm, hookworm,
Enterobius, Trichuris, Strongyloides
and Trichinella spiralis.
• Inhibits the eggs of worms and kills
larvae.
• Symptomatic relief in cutaneous
larva migrans, Trichinella spiralis
larvae, guinea worm disease.
• MECHANISM OF ACTION
• The precise mode of
action of thiabendazole
on
the
parasite
is
unknown, but it most
likely
inhibits
the
helminth-specific
enzyme
fumarate
reductase.
• Thereby inhibiting the
citric
acid
cycle,
mitochondrial respiration
and
subsequent
production
of
ATP,
ultimately leading to
helminth's death.
PHARMACOKINETICS
• It is chelating agent and form stable
complexes with metals including
iron, but does not bind with calcium.
• It can also get absorbed through skin
ADVERSE EFFECTS
• Frequent
• Often interfere with normal activity.
• Nausea, vomiting, loss of appetite,
headache, giddiness are most
common.
• It can impair alertness-driving and
operation of machinery should be
prohibited.
• Itching, abdominal pain, diarrhoea.
CLINICAL USES
• Because of frequent side effects
and poor patient acceptability
used only when other better
tolerated drugs are ineffective.
• strongyloidosis
• Cutaneous larva migrans
• Trichinosis-intestinal infestation
and larvae in muscles
PYRANTEL PAMOATE
•A broad specturm
SPECTRUM:
•Threadworm,
roundworm, hookworm,
Ascaris, Enterobius and
Ancylostoma,
Necator
infestation.
•Less active against
• Strongyloides
•Inactive against
• Trichuris
worms.
and
other
MECHANISM OF ACTION
• Acts as a depolarizing
neuromuscular blocker
• Causes
the
release
of
acetylcholine and inhibits
cholinesterase
• Activation
of
nicotinic
cholinergic receptors in the
worms
• Resulting
in
persistent
depolarization
• Slowly developing contracture
and spastic paralysis.
• Paralyzing the helminthes
• Result of causing the worm to
"lose its grip" on the
intestinal wall and be passed
out of the system by natural
process.
• Worms are then expelled.
ADVERSE EFFECTS
• Infrequent
mild transient GI
disturbance
• Drowsiness,headache, insomnia.
• Rash ,fever
CONTRAINDICATIONS
• Should not be used in liver diseases.
• Pregnancy
• Child under 2 years of age
CLINICAL USE
• Very effective against
luminal organisms.
• Entrobius vermicularis
(pin worm)
• Ascariasis lumbricoids
(common round worm)
• Ancylostoma dudenale
(hook worm)
PIPERAZINE
• Introduced in 1950
• Highly active drug against Ascaris and
Enterobius
MECHANISM OF ACTION
• Causes hyperpolarization of
Ascaris muscle
• By a GABA agonistic action
• Opening Cl- channels
• That causes relaxation and
depresses responsiveness to
contractile action of ACh.
• Flaccid paralysis
• Worms are expelled alive
• It does not affect neuromuscular
transmission in man
CLINICAL USES
• Only recommended for the
treatment of ascariasis cure rate
90%.
ADVERSE EFFECTS
• Safe and well tolerated.
• Nausea,
vomiting,
abdominal
discomfort and urticaria
• Dizziness and excitement occur at
high doses
• Toxic doses produce convulsions;
death is due to respiratory failure.
CONTRAINDICATIONS
•
•
•
•
In epileptics
Impaired liver or kidney functions
Pregnancy
Malnutrition
LEVAMISOLE, TETRAMISOLE
• Tetramisole :- in the late 1960s.
• Recemic; levo isomer (levamisole):more active and is preferred.
SPECTRUM
• Both are active against many
nematodes
• But use is restricted to ascariasis and
ancylostomiasis.
• Strongyloides larvae are killed, but
adult worms are not sensitive.
• MECHANISM OF ACTION
• Two mechanisms:
• The ganglia in worms are stimulated
causing tonic paralysis and expulsion
of live worms.
• Interference with carbohydrate
metabolism (inhibition of fumarate
reductase) may also be contributing.
PHAMACOKINETICS
•
•
•
•
Given orally
Rapidly absorbed
Widely distributed.
Crosses the blood-brain barrier.
ADVERSE EFFECTS
•
•
•
•
•
•
Nausea,
Abdominal pain,
Giddiness,
Fatigue,
Drowsiness
Insomnia
USES
• For Ascaris infestation
• Levamisole is a second line drug
for A. duodenale
• It is less efficacious against
Necator.
DIETHYL CARBAMAZINE CITRATE (DEC)
• Developed in 1948
• It is the first drug for filariasis.
• Piperazine derivative
SPECTRUM
• Highly selective effect on Microfilariae
(Mf).
• Active against Mf of W. bancrofti and B.
malayi, Loa loa, onchocerca volvulus .
MECHANISM OF ACTION
•
•
•
•
Immobilizes microfilariae
Alters their surface structure
Displacing them from tissues
Making them susceptible to destruction
by host defense mechanism.
ADVERSE EFFECTS
• Nausea, loss of appetite, headache,
weakness and dizziness
• A febrile reaction with rash, pruritus,
enlargement of lymph nodes and fall
in BP
• Leukocytosis and mild albuminuria
USES
• Filariasis
• Tropical eosinophilia
• For Loa loa and 0. volvulus infections
IVERMECTIN
• A macrocyclic lactone
MECHANISM OF
ACTION
• Extremely potent semisynthetic
derivative
• Acts on the parasites by binding to a
novel allosteric site on the
• Obtained
from
streptomyces
acetylcholine nicotinic receptor to
avermitilis
cause an increase in transmission
• By opening glutamate-gated chloride
SPECTRUM
• Choice for single dose treatment of
• Onchocerciasis and strongyloidosis.
• Highly effective in
• Bancroftian, brugian filaria,cutaneous larva
migrans and ascariasis,
• Moderate Efficacy against
• Enterobius and Trichuris
• Certain insects, notably scabies and
head lice are killed by ivermectin.
channels
• Chloride influx increased
• Hyper polarization occurs
• Resulting in paralysis of the worm.
MECHANISM OF ACTION
Ivermectin
Targets
GABA receptors of parasite
Chloride ion influx enhanced
Hyper polarization occurs
Paralysis of the worm
ADVERSE EFFECT
• Fatigue, dizziness, GI disturbance
• Nausea
• Abdominal pain
• Pruritis
• Giddiness
• Constipation
• Lethargy
• Transient ECG changes
CONTRAINDICATION
• Other drugs that enhance GABA
• e.g
Barbiturates,
valproaic acid.
bnezodiazepines,
• Pregnancy
• Imparied blood brain barrier
• Children under 5 years of age.
USES
•
•
•
•
•
Filariasis
Strongyloidosis
Other intestinal nematodes
Scabies
Pediculosis
NICLOSAMIDE
• Highly effective
MECHANISM OF ACTION
• Inhibition of oxidative
• Useful drug for treatment of tape
phosphorylation
in
worm (cestodes) infestation
mitochondria
• Safe during pregnancy.
• Interference of anaerobic
SPECTRUM
generation of ATP by
• Against cestodes infesting man –
tapeworm.
Taenia
saginata,
T.
solium,
• Injured worms are digested
Diphyllobothrium
latum
and
or expelled (purgation)
Hymenolepis nana, as well as
threadworm.
ADVERSE EFFECT
• Well tolerated
• No systemic toxicity
• Minor
abdominal
symptoms
• Malaise
• Pruritis
• Diarrhea
• Light headedness
• Safe during pregnancy
and in patients with poor
health.
CLINICAL USES
• T.Saginata (Beef tape worm)
• T.solium (pork tape worm),
• Diphyllobothrium
latum
(fish
tape worm)
• Hymenolepis
nana:
It
effective against adult parasite
is
PRAZIQUANTEL
• Novel anthelmintic
• Wide
ranging
activity
against
Schistosomes, other trematodes,
cestodes and their larval forms but not
nematodes.
• Effective against wide variety of
cestodes and tremetodes.
• SCHISTOSOMIASIS
- LIVER FLUKES
- LUNG FLUKES.
• Taeniasis
• Neuro Cysticercosis
MECHANISM OF ACTION
• Rapidly taken up by worms.
• Leakage of intracellular Ca++
causing paralysis.
• Worms
lose
grip
on
intestinal wall including
tissues and veins.
• Acts against all stages of
worm including larvae.
PHARMACOKINETICS
• Absorption is enhanced with
food.
• Crosses blood-brain barrier
ADVERSE EFFECT
• Bitter in taste
• Nausea
• Abdominal pain
• Headache
• Dizziness and sedation
• Rashes, fever, itching and
body pain
CLINICAL USES
•
•
•
•
•
•
Tapeworms
T. saginata, T. solium
H. nana, O. latum
Neurocysticercosis
Schistosomes
Other flukes
THANK YOU
-PHARMA STREET