5. Anti-helminthics Flashcards
Describe the classification of helminths
- Nematodes (roundworm)
- Blood and tissue
- Intestinal - Cestodes (tapeworms)
- Taenia (human host)
- Echinococcus (human is an accidental host) - Trematodes (flukes)
- Lungs
- Liver
- Blood
4 main pathological mechanisms of helminths
Inflammation
Competition for nutrients
Space occupying lesions
Stimulation of fibrosis
Name 4 Nemotode helminths found in the intestines
Ascaris
Hookworm
Enterobius
Trichiuris
Transmission of helminths?
Faecal-oral
Vector
Direct invasion
4 types of host?
Definitive
Intermediate
Accidental
Parathenic
4 examples of helminth vector?
Flies, Aedes mosquito, crysops and snails
What is the consequence of repeated cycles of inflammation and bacterial infection in acute lymphoedema?
Elephantiasis
Clinical features of trichiuris?
• Vague abdominal symptoms • Trichiuris dysentery syndrome • Growth retardation • Intellectual compromise -micronutrient deficiency -mucosal integrity
Clinical features of hookworm?
Anaemia due to blood usage
Vague abdominal pain
Ascaris clinical features?
Vague abdominal pain
Intestinal obstruction
Hepatobiliary obstruction and jaundice
Competition for nutrients, name 4 helminthis in which this is their main pathological mechanism?
- Hookworms
- Ascaris
- Tapeworms
- Trichiuris trichiura
Space occupying lesions?
- Eggs in the wrong place
- Cysticercosis causing CSF obstruction
- Ascaris causing intestinal obstruction
What pathology’s are caused by parasites being in the liver, brain and CSF
Cysticercus causing CSF block
Hydatid cyst in the liver
Cerebral cysticercosis in the brain (leading to seizures)
What is the consequence of schistosomiasis?
In schistosomiasis, eggs trapped in the tissues produce granulomatous inflammatory reactions, fibrosis, and obstruction.
What is the result of fibrosis associated with tissue schistosomes?
Leas to inflammation and fibrosis….
Lung fibrosis –> Right HF
Liver fibrosis –> Portal hypetension
Bladder fibrosis –> Bladder cancer
What is the general treatment for helminth infections associated with the following pathogenesis: • Inflammation • Competition for nutrients • Space occupying lesions • Stimulation of fibrosis
Inflammation
• Anti-inflammatory eg., steroids
Competition for nutrients
• Reduce worm burden and support nutrition
Space occupying lesions
• Surgery, decompression
Stimulation of fibrosis
• Helminth eradication and treatment of secondary effects
Treatment of cestode classified helminths?
Praziquantel
Due to the problems of the cysticercosis, what must be combined with anti-helminthic treatment of cestodes?
Continue anti-epileptic drugs
+ Steroids
Treatment of nematodes classified helminths?
Albendazole mainly
[Levamisole and piperazine are rarely used]
Praziquantel: Mechanism? Treats which diseases? Properties? Side effects on neuro, GI, Liver and skin? Drug interactions?
Mechanism: Probably increases calcium permeability of membranes depolarising them. May interfere with purine synthesis
Treats: • Hydatid disease • Cysticercosis • Schistosomiasis • Clonorchis, Fascioliasis and Paragnomiasis infection
Properties:
- Well absorbed orally
- Low systemic conc
- Excreted in the kidneys
- Short half life
Side effects:
Neural: Dizziness, headache, drowsiness and somnolescence
GI: Abdominal cramps and nausea. Diarrhoea
Liver: Transient asymptomatic rise in transaminases
Skin: Urticaria, rash and pruritis
Drug interactions:
Interacts with rifampicin (decreased concentrations), carbamazine, phenytoin (reducing praziquantel bioavailability)
Albendazole: Classification? Used for treatment of which nematode? Used for treatment of which protozoa? Used for treatment of which Cestoda infections? Mode of action? Where is it concentrated? Side effects?
Classification: A benzimidazole
Treatment of nematode infections: trichiuriasis, filariasis, Enterobius infection, ascariasis, hookworm, toxocariasis, strongyloidiasis
Treatment of some protozoa: giardia
Treatment of some cestode infections: Neurocysticercosis
and hydatid disease
Mode of action:
- Binds to colchicine sensitive receptor or tubulin. Prevents polymerisation into microtubules.
- Impaired glucose uptake and depleted glycogen stores
- Degenerative changes appear in the worm
Concentrated in semen and may be teratogenic
Side effects: • Persistent sore throat • Headaches dizziness and seizures • Acute liver failure • Aplastic anaemia and marrow suppression
Piperazine as a treatment for helminths?
- Agonist activity against the gamma butyric acid receptor paralysing muscular activity
- Orally active
- Metabolism in liver
- Variable half life
- Used to treat ascariasis and enterobius infection
- SE include GI tract upset and rarely hypersensitivity, dizziness
What drug replaces levamisole and pyrantel
Albendazole as it’s less toxic
Helpful use of diethyl carbamazine?
Causes worms to come to skin surface for diagnosis by biopsy.
Features:
• A piperazine derivative
• WHO essential medicine list
• Inhibits arachidonic acid making parasites more susceptible to immune attack
• Filaria infection
• Associated with increase in inflammation: caution Mazzotti reaction, loss of site in onchocerciasis
Ivermectin: Mode of action? Active against? Complicated by? How is absorption increased pass the BBB?
- Ivermectin binds glutamate-gated chloride increase in the permeability of the cell membrane to chloride ions with hyperpolarization of the nerve or muscle cell resulting in paralsysis and death of the parasite either directly or by causing the worms to starve.
- Active against fliarial worms, lice, scabies and bed bugs
- Complicated by CNS depression
- Increased risk of absorption past the blood brain barrier of HIV protease inhibitors, calcium channel blockers and glucocorticoids
Niclosamide:
Mechanism?
Treats?
Side effects?
Mechanism: Inhibits glucose uptake, oxidative phosphorylation and anaerobic metabolism
Treats: Used for the treatment of tape worm infections only
Side effects: Causes dizziness, skin rashes, drowsiness and perianal itching.
Prevention and control of intestinal helminths
- Vector control for filariasis
- Meat inspection for cysticercosis
- Sanitation and hygiene for intestinal nematodes
Examples where inflammation
is the main pathogenic mechanism
- Filariasis
- Onchocerciasis ( in eye leading to blindness)
- Toxocariasis (generalised inflammation all over body)
- Cysticercosis
- Schistosomiasis
- Enterobius
How many lobes should a neutrophil have? Pathology leading to excess lobes?
Should have 4
If more, sign on anaemia
Cells in the stomach involved in gastric acid production
The stomach has a mucus cell lining, parietal glands an pyloric glands.
The parietal cells secrete HCl, pepsinogen, IF, mucus.
Whilst pyloric glands secrete mucus for protection and gastrin which stimulates ECL cells.
3 modes of transmission of helminths?
Faecal oral (Ascaris) Vector (filariasis) Direct invasion (Schistosomiasis)
