Anti Parasitics And Role In Parasite Control Flashcards
Why is veterinary parasite chemotherapy important
In absence of a vaccine it is the only treatment method
What is environmental engineering
Attempt to reduce parasite eggs in enviornemnt - expensive
What is vector control
Target mediate shot of some parasites
What is biological control
Using insecticides
What is the issue of using insecticides
Molecules can have toxic side effects on species of animals as well as parts of the environment
What is the biological control of nematodes
Etamotde eating fungi - eats nematodes
Nematodes that eat other nematodess
What do we use for chemotherapy
Chemicals are used for parasite chemotherapy - it is dangerous
What are the principles of parasite chemotherapy?
Selectivity drug must affect parasite and not host - must kill parasite and not host
Chemotherapeutic index - higher than index the safer the drug, lower the index the more toxic of the drug
What are the potential mechanisms of parasite drug selection
Uptake or secretion of drug
Detoxification of drug
Activation of drug
Importance of drug target
Biochemical target
Unique target
What is the uptake or secretion of drug
Kill parasite in the intestine to keep host safe
What is detoxification of drugs
Host can detoxify or metabolise drug but the parasite hasn’t got the ability to do this
What is activation of drug
Some drugs are given in a form that needs to be activated to work such as host stomach activates the drug before it reaches the parasite
What is the importance of drig target
So protein target is more important for parasite survival to host survival meansing that’s host can use a different biochemical target to kill parasite
What is binding to drug target
Drug may bind better to a parasite protein than a host protein
What are current problems with current anti-parasitic agents
Re-infection in endemic areas
Some drugs expensive
Few have serious side affects
Resistance
Nvironmental resisdue issue
What is the ideal anti-parasitic
Efficient against all parasitic stages of a species
Broad spectrum against man species
Non=toxic to host and environment
Metabolised and excreted by host
Easily administered
Reasonable cost
What is the mode of action of levamisole
Agonists or antagonist thatch to acetcholine receptors of nematodes
Agonists = nematode loses acitvity as it enhances receptor activity
Antagonist = nematode stops working completely
What is the importance of understanding parasite resistance
Only a limited number of effective and safe antiparasitic agents commercially available
Development of new drugs slow and resistance can rise rapidly
What is parasitic resistance
The genetically transmitted bias of sensitivity i parasite populations previously sensitive to same drug
Drugs are getting restart such as river fluke
What are the pharmacological mechanisms of parasite drugs
Loss of drug uptake mechanisms
Loss or modification of target site - due to mutation?
Parasite ompensate for loss of target activity - parasite found new biochemical pathway
Improved parasite detoxification pathway
Why is tublin a makjor Benzimidazole target
Blocks assembly of tublin into microtubules
Cascade of changes causing a loss of cell homeostasis
Microtubules required for cell division, cell movement, cell shape - cascade of changes will block the assembly - cell blocks up
What is the mode of action of benzimadzole on microtubules
Causes local unfolding in the tublin stoppin the tublin to join up
What is the pharmacological selectivity of benzimidazoles
Binds both host and nematode tubulin
What are the 2 groups of BZs
More inhibitory to parasite tublin - good
Inhibit parasite and mammalian tubulin with apparen same affinity - bad group
What is the nature of mebendazole selectivity
Revealed by radio-labelling techniques
Mebendazole nematode tublin complex - more stable- this is why it disrupts nematode tublin and not host tublin
Highlights complexities in drug activists
Hy is there wide spread resistance to benzimidasoles in veterinary nematodes
Tubulin from resistant nematodes reduced affinity for BZs
How has the resistance to benzimidazoles occured
Structure changes in nematode tubulin targets as mutations in restraint nematode tubulin
Modification in nematode phase 3 drug pumps in membranes
What is the mechanisms of benzimidazoles restiance at tubulin target
Tublin is cloned and sequence from resistant/sensitive nematodes - looks for differences in air acid strucutre
How does benzimidazoles bind to target
Tubulin are built from amino acids coming from parts of the protein - resistance can be scattered across this protein
One nematode can have one mutation while another can have a different mutation
This means that the drug must me multi-complex to deal with the mutations
