ANTHELMINTIC DRUGS

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ANTHELMINTIC DRUGS

• DR.ABDUL LATIF MAHESAR
• Department of Medical Pharmacology
• KSU

Pharma Team
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Nematodes

• A) INTESTINAL ROUND WORMS
• Ascaris lmubricoides (common round worm)
• Enterobius vermicularis (pinworm)
• Trichuris trichuria (whipworm)
• Strongyloids stercoralis (threadworm) ?
  Strongyloidiasis
• Ancylostoma duodenale Necator americanus
  (hookworm)

• B) TISSUE ROUND WORMS
• Trichinella spiralis. (Trichinosis)
• Dracunculus medinensis (guineaworm) ?
  Dracunculiasis

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Other round worms

• FILARIAE, includes
• Wuchereria bancrofti (filariasis)
• Loa loa (loiasis)
• Onchocerca volvulus (onchocerciasis) River
  blindness.
• Brugia malayi and B. timori

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• Cestodes (tape worms)
• Tenia saginata (Beef tapeworm)
• Tenia solium (Pork tapeworm),
• Cysticercosis (Pork tapeworm larval stage)
• Hymenolepis nana (Dwarf tapeworm)
• Diphyllobothrium latum (Fish tapeworm)

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Hydatid tape worm

• Echinococcus species

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TREMATODES/FLUKES (leaf-like)

• Schistosoma mansoni
• Schistosoma hematobium
• Schistosoma Japonicum
• Paragonimus species ? Paragonimiasis
• Fasciolopsis buski
• Fasciola hepatica
• Clonorchis sinensis

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ANTIHELMINTIC DRUGS

• BENZIMIDAZOLEs
• 1.ALBENDAZOLE
• It possess broad-spectrum activity . It is the
  drug of choice for treatment of
• Hydatid disease and
• Neurocysticercosis.
• It is also a major drug the treatment of
  (intestinal nematodes)
• Ascariasis,
• Trichuriasis,
• Strongyloidiasis,
• Enterobius vermicularis (pinworm),
• Nector americanus, Ancylostoma duodenale
  (Hookworms) infections.

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Albendazole contd

• Mechanism of action
• Inhibits microtubule synthesis and glucose uptake
• It has larvicidal effects on hydatid disease,
  cysticercosis, ascariasis, and hookworm
  infection.
• Also, ovicidal in ascariasis , ancylostomiasis
  (hookworm), trichuriasis

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Pharmacokinetics of Albendazole

• It is a benzimidazole carbamate
• It is administered orally, and absorbed
  erratically (unpredictable), absorption can be
  increased with fatty meal.
• It is metabolized in the liver rapidly to its
  active metabolite albendazole sulphoxide. (1st
  pass metabolism)

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Contnued

• It has a plasma half life of 8-12 hours
• Sulphoxide is mostly (80) protein bound ,
  distributed to the tissues and enters the bile,
  cerebrospinal fluid, and the hydatid cyst.
• urinary excretion

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Clinical uses of albendazole

• It is administered on empty stomach when used
  against intraluminal parasites but with fatty
  meal when against tissue parasites.
• Ascariasis, trichuriasis, hookworm, pin worm
  infection (intestinal)
• Acheives 100 cure in pinworm
  infection and high cure rates for others or
  marked reduction in eggs counts.

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• 2. Hydatid diseases
• Drug of choice, with meals.
• Bone cyst may require treatment for 1 year.
• If patients are to be treated surgically, both
  albendazole and praziquantel are used
  preoperatively for one month to reduce cyst fluid
  leakage. After surgery albandazole should be
  continued for a whole month.

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Albendazole contd

• Neurocysticercosis It is the drug of choice.
• It is effective for symptomatic
  parenchymal and interventricular cysts. Less
  effective in arachnoid cyst.
• It is superior to Praziquantel for
  neurocysticercosis for the following
• Shorter course of treatment.
• It is cheaper
• It is co-administeration with steroid increases
  its absorption
• It is better in penetration arachnoid space..
• It is also effective for ocular cysts.
• Other infections Drug of choice in cutaneous and
  visceral larvea migrans , intestinal
  cappillariasis, microsporidial infections,
  gnathostomiasis, trichinosis, clonorchiasis,
  opisthorchiasis, toxocariasis, and loiasis.

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• It is used along with cotricosteroid to decrease
  the inflammation caused by dying organism, and it
  also reduces the duration of course
• During the acute phase of cysticercotic
  encephalitis, albandazole is contraindicated and
  corticosteroid is indicated instead.
• N.BIn intestinal nematodes, treatment in days
• But in hydatid disease Neurocysticercosis, the
  treatment take longer duration

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Albendazole cond

• Adverse effects
• In short term use there is no significant
  adverse effects.
• In long term use abdominal distress, headache,
  fever, fatigue, alopecia , increased liver
  enzymes , pancytopenia. Blood counts and LFT
  should be carried out regularly.
• Not given during pregnancy and in hypersensitive
  people.
• Safety in children is not established in children
  below 2 years of age.

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MEBENDAZOLE (Vermox)

• it is a synthetic benzimidazole
• it has wider spectrum and is safe
• Mechanism of action Similar to albendazole
• Effecacy influenced by GI transit time,
  intensity of infection, and strain of parasite.
• It is also used to kill hook worm, pin worm ,
  ascaris and trichuris eggs.

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Mebendazole cont

• Pharmacokinetics
• Less than 10 of orally administered drug is
  absorbed
• Absorption increases with fatty meals
• Absorbed drug is 90 protein bound
• It is converted to inactive metabolites rapidly
  in liver.
• It has half life of 2-6 hours
• It is primarily excreted in bile.

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Mebendazole cont

• Clinical uses
• It is taken orally before or after meal, tablets
  should be chewed before swallowing.
• Ascaris lumricoides , trichuris trichura ,
  hookworm and trichstrongylus It is useful drug
  in case of mixed infection by these parasites.
• in adults and children over 2 years cure rate is
  90-100 except hookworm but a marked reduction
  in worm burden occurs

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Mebendazole contd

• Intestinal cappilliaris
• Trichinosis It has limited efficacy against
  adult worm.
• Corticosteroids coadministered in sever infection.

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Mebendazole cond

• Adverse effects and precautions
• No adverse effects in short term therapy except
  for mild GI disturbances.
• With high dose? hypersensitivity reactions,
  agranulocytosis , alopecia, elevation of liver
  enzymes.
• Contraindicated in pregnancy.
• Used with caution under 2 years of age may cause
  convulsion in this group.
• carbamazepine or phneytoin ? ? conc. Cimetidine
  ? ? conc.
• used with caution in cirrhosis

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Thiabendazole

• It is benzimidazole. It is tasteless and
  insoluble in water.
• It is a chelating agent and forms stable
  complexes with metals including iron but does not
  bind with calcium.
• It is rapidly absorbed orally
• It has half life of 1.2 hrs
• It is completely metabolized in liver and 90 is
  excreted in urine
• It can also get absorbed through the skin. Thus,
  could be applied in creams.

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Thiabendazole cond

• Mechanism of action similar to other
  benzimidazoles.
• It is ovicidal for some parasites.
• It also possesses immunosuppressive, antipyretic,
  and mild antifungal and scabicidal (destroying
  the itch mite causing scabies ) effects.

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Clinical uses

• Should be given after meals and tablets should be
  chewed
• For strongyloides (threadworms) infectionscure
  rate is 93
• For cutaneous larval migrans thiabendazole
  cream is effective and applied topically or
  given orally
• Also effective for intestinal capillariasis and
  scabiasis.

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Thiabendazole contd

• Adverse reactions and contraindications
• It is more toxic than other benzamidazoles
• GI disturbances
• Pruritus, headache, drowsiness, neuropsychiatric
  symptoms rarely may cause tinnitus, bradycardia,
  hypotension, hyperglycemia, convulsions,
  neutropenia and other adverse effects may occur.
• Irreversible live failure.
• Fatal StevensJohnson syndrome (inflammation of
  the skin)
• Not used in children below the weight of 15 kg,
  during pregnancy, hepatic and renal diseases.

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PYRANTEL PAMOATE

• It is a broad-specturm antihelminthic
• It is not effective against trichuriasis
  (whipworms) and trichostrongylus orientalis
  infections, yet oxantel pamoate is considered
  effective against trichuriasis. Both drugs can be
  combined for their synergistic effect.
• Pharmacokinetics
• It is poorly absorbed orally. Active mainly
  against luminal organisms.
• Half of the drug is excreted unchanged in the
  feces.
• Mechanism of action
• It is a depolarizing neuromuscular blocking agent
  that causes release of acetylcholine and
  inhibition of cholinesterase leading to the
  paralysis of worms followed by their expulsion
  from the GIT.

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Pyrantel pamoate (contd)

• Efficacy and clinical uses
• it is very effective against mature and immature
  luminal organisms, but not effective against
  migratory stages in the tissues or against ova
• Enterobius vermicularis (pinworm).
• Ascaris lumbricoids (common roundworm)
• Ancylostoma duodenale (hookworm) single dose for
  light infection but a 3-day course is necessary
  for heavy infection especially N americanus
  infection.

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Pyrantel pamoate contd

• Adverse effects are infrequent and mild.
• GI disturbance
• Drowsiness, headache ,insomnia.
• Rash, fever
• Contraindications
• Should not be used in liver diseases.
• Pregnancy
• In children under 2 years of age

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PIPERAZINE

• Only used for the treatment of ascariasis.
• It is readily absorbed orally and excreted in
  urine
• Mechanism of action
• It causes paralysis of ascaris by blocking
  acetylcholine at the myoneural junction,
  expelling the live worm by normal peristalsis.

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Piperazine contd

• Treatment is continued for 3-4 days or
  repeated after one week in case of heavy
  infections.

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Piperazine contd

• Adverse effects
• GI disturbances
• Neurotoxicity, allergic reactions serum sickness
  like syndrome
• Contraindications
• Epilepsy or chronic neurologic disease
• Impaired liver or kidney functions
• Pregnancy
• Malnutrition

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Drugs used for treating human intestinal
nematodes (single dose unless otherwise stated

• Ascariasis Hookworm enterobius
  tricuris strongyloides
• Piperazine
  -
  -
• Pyrantel pa
  -
  -
• Albendazole
  
  
• Mebendazole
  
  
• Thiabendazole n/a n/a
  n/a n/a
  
• Ivermectin n/a n/a
  n/a n/a
  

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Drug treatment for tape worm(cestodes) infection

• Niclosamide
• Praziquantel
• Albendazole

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NICLOSAMIDE

• It is useful for the treatment of adult tape
  worm (cestodes) infestation
• Mechanism of action
• Adult worm is rapidly killed by inhibition of the
  oxidative phosphorylation or stimulation of
  ATPase activity.
• has no effect on ova
• Pharmacokinetics
• It is not absorbed from the gut
• Neither drug nor its metabolites are found in
  the blood or urine.

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Niclosamide contd

• Clinical uses
• T. Saginata (Beef tape worm),T. solium (pork
  tapeworm), Diphyllobothrium latum (fish tapeworm)
• In case of T. solium after 2 hrs of treatment,
  purge of magnesium sulphate should be given to
  eliminate all
• mature segments.
• Not effective against cysticercosis or hydatid
  disease. b/c
• its not absorbed from the gut
• Hymenolepis nana
• H diminuta and Dipylidium caninum
• Alternative for Fasciolopsis buski, Heterophyes
  heterophyes, Metagonimus yokogawi.

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Niclosamide contd

• Adverse effects
• Mild, infrequent and transitory GI disturbances
• Alcohol consumption should be avoided
• Not indicated in children under 2 years of age
  or pregnancy.

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Diethylcarbamazine

• The drug of choice for the treatment of
  filariasis, loiasis and tropical eosinophilia.
• Pharmacokinetics
• It is a synthetic derivative of piperazine
• Rapidly absorbed from the gut
• It has a half life of 2-3 hours which increases
  in alkaline urine up to 10 hours.
• Equilibrates with all tissues except fat
• It is excreted in urine unchanged.
• Dosage is reduced in urinary alkalosis and renal
  impairment.

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DIETHYLCARBAMAZINE cond

• Mechanism of action
• It immobilizes microfilariae in tissues and
  alters its surface structure, making them more
  susceptible to destruction by host defense
  mechanism
• Unknown mechanism against adult worms
• It also possesses an immunosuppressive effects
• It has no teratogenic effects on experiment
  animals

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DIETHYLCARBAMAZINE cond

• It is a drug of choice for the treatment tissue
  cestodes,
• W. bancrofti, B. malayi, B. timori, and Loa
  loa.
• Microfiliariae are rapidly killed. Adult worms
  are killed slowly requiring several courses of
  treatment. Adult worms are either killed or
  sterilized.
• It is highly effective against L. loa.

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DIETHYLCARBAMAZINE cond

• Anti histamines and corticosteroids are given in
  allergic manifestations.
• Complete Cure may be require several courses of
  treatment over 1-2 years.
• The drug may be used in prophylaxis for loiasis,
  bancroftian, and Malayan filariasis
• Tropical (pulmonary) eosinophilia
• Mansonella streptocerca

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DIETHYLCARBAMAZINE cond

• Drug induced/ Reactions induced by Dying
  parasites
• Fever , malaise, papular rash, headache, GI
  disturbance, cough, chest, muscle, joint pain
• Leukocytosis, proteinurea, ? eosinophilia
• Retinal hemorrhage
• Encephalopathy
• Lymphangitis and lymphadenopathy.

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DIETHYLCARBAMAZINE cond

• Contraindications and cautions
• Hypertension
• Renal disease
• Patient suspected of having malaria
• Patients with lymphangitis

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IVERMECTIN

• It is the drug of choice for treatment of
  strongyloidasis and onchocerciasis
• It is a macrocyclic lactone
• It is used orally and is rapidly absrobed,
  possesses wide volume of distribution about 50 L.
• It has a half-life of 16 hrs
• It is exclusively excreted in feces

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IVERMECTIN contd

• Mechanism of action
• It intensifies GABA mediated transmission of
  signals in peripheral nerves ? paralyzing the
  worm.
• In onchocerciasis it is microfilaricidal. It
  does not kill the adult worm

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IVERMECTIN contd

• Clinical uses
• Onchocerciasis with the 1st treatment, patients
  with microfilariae in the cornea or anterior
  chamber may be treated with corticosteroid.

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IVERMECTIN contd

• Strongyloidiasis in immunosuppresed patient,
  repeated treatment is often needed.
• Bancrofti filaricidal as it is mirofilaricidal
• It is also used for scabies, lice, and cutaneous
  larva migrans.
• Eliminates adcarid worms
• Reduces microfilariae in Brugia malayi and M
  ozzardi.

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IVERMECTIN contd

• Adverse effects
• Fatigue
• dizziness,
• GI disturbance
• In Onchocerciasis
• Mazotti reaction fever, headache, dizziness,
  somnolence (state of being drowsy), weekness,
  rash ,diarrhea, arthralagia, hypotension,
  lymphadenitis, peripheral edema due to killing of
  microfiliariae, for this steroids may be
  necessary for several days
• Swelling and abscess at site of adult worm
• Punctuate corneal opacities.

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IVERMECTIN cond

• Contraindication
• other drugs that enhance GABA activity e.g
  Barbiturates, bnezodiazepines, valproic acid.
• pregnancy
• Impaired blood brain barrier
• Children under 5 years of age.

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BITHIONOL

• It is the drug of choice for the treatment of
  fascioliasis (sheep liver fluke)
• It is also used as an alternative for
  praziquantel in treating pulmonary paragonimiasis
• Repeat doses in case of cerebral paragonimiasis.
• Pharmacokinetics
• It is orally administered and excreted in urine.

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BITHIONOL

• Adverse effects
• GI disturbance
• Dizziness,headache
• Pruriuts ,urticaria,Leucopenia
• Contraindications and precautions
• hepatitis,
• leucopenia
• Used with caution under 8 years of age.