Revision Mechanisms of action Flashcards
Outline the ideal antiparasitic drug?
- Effective in removing adult and immature forms of parasites from the body,
- A wide therapeutic index (the toxic dose is at least three times the therapeutic dose),
- Easy to administer e.g. in feed, injections, and pour-on, (iv) inexpensive or economically justifiable,
- No residue problems, especially in food-producing animals (residues are not an issue in non-food animals),
- Provides specific advantages in terms of pharmacokinetics and/or metabolism (e.g., more convenient dosing regimen, improved drug interaction profile, etc
Outline the mechanism of action of antiparasitics which cause paralysis of parasites via mimicking the action of neurotransmitters:?
Paralysis of parasites via mimicking the action of neurotransmitters:
- Acetylcholine (Ach), gamma-aminobutyric acid (GABA), glutamate (Glu), octopamine (OA), serotonin (5-HT)
- These neuropeptides (excitatory or inhibitory) can be present in more than one parasite category (i.e. nematodes, cestodes, trematodes, and/or arthropods)
Outline the mechanism of action of antiparasitics which alter metabollic processes?
Alteration of metabolic processes
- Inhibition of microtubule synthesis
- Uncoupling of oxidative phosphorylation
- Inhibition of folic acid synthesis/metabolism
- Inhibition of thiamine utilization
- Inhibition of chitin formation in arthropods
- Simulation of insect juvenile hormones
- Ion gradients/membrane potential
- Inhibition of protein synthesis
- Inhibition of DNA synthesis Mechanism of action of antiparasitics
Outline the mechanism of action of antiparasitics which alter parasite reproduction?
Alteration of parasite reproduction
- Inhibition of egg production in nematodes
- Inhibition of multiplication in protozoa
Note, not an anthelmintic action; this is a consequence of an anthelmintic action
Outline white, yellow, clear and orange drenches?
Outline types of antiparasitics?
Endoparasiticides (internal antiparasitics)
kill parasites living inside the animal, such as gastrointestinal parasites, respiratory parasites and heartworms. Endoparasiticides include anthelmintics (agents lethal to worms) and antiprotozoal (agents lethal or suppressive to protozoa)
Ectoparasiticides
(external antiparasitics) kill parasites living on the outside of an animal, including fleas, ticks, mites an dlice
Endectocides
these combine the activity against internal and external parasites, offering greater convenience and broader-spectrum metazoan parasite control
Describe the mode of action of Benzimidazoles?
Mode of action:
bind to tubulin molecules leading to inhibition of polymerization and disorders of intracellular homesostasis.
Describe benzimidazoles resistance?
Via genetic changes in the drug target.
- Benzimidazoles resistance is associated with several single-nucleotide polymorphisms (SNPs) in the drug’s target molecule β-tubulin isotype 1, the most common SNP being a phenylalanine to tyrosine substitution at position 200 in the gene
- A single nucleotide change can lead to an amino acid substitution in the drug target protein and so change the affinity of the drug for the target.Such a change influences the response to the drug and might cause the drug to be less effective
Describe levamisole mode of action?
Mode of action:
- affect NICOTINIC acetylcholine(nAch) receptors. Via mimicking Ach action they change permeability of the post-synaptic membrane, leading to depolarisation and spastic paralysis of theworms.
- Round, hook and whip worm in dogs and Aelurostrongylus abstrusus in cats
- Immunostimulant in some species
- Toxicity in some dogs
Discuss macrocyclic lactones?
The first class of endectocides
In both arthropods and nematodes
Cestodes, trematodes and adult heart worm are insensitive
Two groups:
Avermectins (ivermectin, selamectin, doramectin)
Milbemycins (milbemycin, moxidectin)
COLLIES sensitivity to ivermectin:
- Signs include mydriasis, tremor, ataxia, emesis, salivation, coma
- Deficient in P-glycoprotein
- Selamectin–Safe for collies
Macrocyclic lactones mode of action?
Hyper-polarisation (inhibition) also, affect GABA-gated Cl-channels in the CNS of both vertebrates & invertebrates Protected in vertebrates by P-glycoprotein transmembrane transport pump.
What is the mode of resistance to macrocyclic lactones?
Describe mode of action of monepental?
Mode of action: The nematode needs normal MPTL-1 receptors for its nervous system, so it can co-ordinate its movement.
Monepental is a direct agonist of the mptl-1 channel, which is a homomeric channel belonging to the DEG-3 family of nicotinic acetylcholine receptors. Binding of monepantel to the receptor results in a constant, uncontrolled flux of ions and finally in a depolarization of muscle cells, leading to irreversible paralysis of the nematodes. These receptors are unique in that they are found only in nematodes.
Discuss emodepside?
Cyclo-octadepsipeptides
- Profender (emodepside/praziquantel)
- Acts on a specific class of transmembrane G-protein coupled receptors (depsiphilins) latrophilin receptor class
- Flaccid paralysis of pharynx
Discuss cestocides?
Cestocides
- Praziquantel
- Binds to b -subunit of voltage gated calcium channels
- Some helminths do not have this subunit – fasciola sp –not susceptible
- Spastic and tetanic muscle contractions
- Vacuolation of the tegument
- Key component of Echinococcus eradication
How do you detect drug resistance?
