BIOL123 - L10

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  • Created by: Katherine
  • Created on: 02-06-16 21:29
There are a limited number of drugs to control viruses, protists and worms. Why?
Because viruses use host enzymes and pathways. Eukaryotic pathogens are Eukaryotic. Drugs that control viruses and eukaryotic pathogens often affect eukaryotic host cells. Drugs must preferentially affect common pathways or targer unique aspects of p
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What are characteristics of the ideal drug?
Selectively toxic to microbe, microbiocidal rather than micrbistatic, stable in vivo, readily delivered to site of infection (how easy is it to access the site, can it be tablet form, inexpensive, not subject to resistance
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What is a suggested drug treatment for Malaria?
Quinine
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What is quinine?
It was extracted from the bark of the chinchona tree.
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After WW2, Quinine was replced by snthetics drug such as ...
Chloroquine
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Why is chloroquine better?
Because it is safer, more effective, easier to make
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Chloroquine is effective against.
All forms of malaria. It has few side effects at a low cost.
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What is the mode of action of Chloroquinine?
Intraceulluar parasire (trophozoite stage) digests haemoglobin - source of amino acids). Digestion takes place inside the pllasmodium food vacuole (generates free haem which is toxic to malaria.
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What happens to chloroquinine inside the vauole?
It concentrates - this interferes with haemozoin formation - the haem remains highly toxic and kills the parasite.
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Why does chloroquine concentrate in food vacuole?
It is a lysocomotropic drug: it is a weak base, uncharged at neutral ph but at acidic pH it carries a positive charge. Uncharged CQ diffuses rapidly throguh the parasite plaams. The food vacuole becomes acidified and chloroquine becomes charged=trap
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What is CQ resistant by?
P.falciparium.
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What caused CQ resistance?
Incomplete complicance, sharing of drugs. Parasite not killed - opportunity to become resistant
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What is the biochemical mechanisms of drug resistance:
Drug inactivation, target bypass (you skip a stage to reach the end product) target modification, increased efflux or decreased influx.
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What are PfCRT?
Chloroquine resistant transporter - it is a 10 transmembrane domain protein located in FV membrane - mutations lead to increased export of CQ from FV
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Even though there is large resistance to CQ is the drug still useful?
Yest, it can be used for other malaria. CQ may regain efficacy against P.falciparium in areas where CQ Usages has been tightly regulated - withdrawla of CQ in dramatic decrease in prevalence of CQ resistant parasites.
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What happens if you stop putting pressure on the CQ resistant parasites?
You see a decrease in the prevalance of CQ resistant parasites
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What is another drug effective against Malaria?
Tetracycline - it blocks transmission by binding to 30S subunit of the prokaryotic ribosome - no effect on eukaryotic ribosomes.
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What is the apicoplast?
It retains own reduced genome - some apicoplast genes have been transferred to the nucleus. Apicoplast encoded genes involved in housekeeping functions or unknown functions. Apicoplast transcriptions and translation = prokaryotic.
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What drug is good against nematodes?
Mebendazole - it binds to B tubulin and inhibits microtubule assemply. Impaired uptake of glucose by larval and adult stages.
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What is a good mediation to treat Ascaris?
Ivermectin - it binds with high affinity to gluatate gated chloride cannels which occur in invertebrate nerve and muscle cell.
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What is the drug of choice against trematodes and cestodes
Praziquantel - has few side effects, has few contraindications, is not effective agianst larval,
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The observed efects of the drug include:
Imcrease in cell membrane permeability, creation of an imbalance in ion transport, loss of intracellular calcum.
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Schistosome control:
Imprementation of the chemotherapy programmes, community vs targeted approach,
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What is the targeted approach?
Treat only symptomatic individuals
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What is the community approach?
Treat everyone
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When would you use targeted
Prevalence is low and the budget is limited
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When would you use community?
The transmission rate is high and there are no budget constraints
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Who are the targeted populaton in schistosomiasis?
School children. These children include the most heavily infected individuals becuase they're most likely to come into contact with the infected water. They benefit most from chemo as they haven't developed the worst stage of infection
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Whats another reason children should be targeted?
They contribute most to transmission. Easily accessible through schools so its possible to caputre the population.
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Is re-infection is very common?
Yes - snails. Repeated chemotherpay is often required. Chemotherapy does not always kill adults but just surpresses egg production. Incomplete complicance leads to sub optimal drug concentration.
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What are characteristics of the ideal drug?

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Selectively toxic to microbe, microbiocidal rather than micrbistatic, stable in vivo, readily delivered to site of infection (how easy is it to access the site, can it be tablet form, inexpensive, not subject to resistance

Card 3

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What is a suggested drug treatment for Malaria?

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What is quinine?

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After WW2, Quinine was replced by snthetics drug such as ...

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