Parasitology 4 Flashcards

Question

Tetrahydropyrimidines pharmakokinetic characteristics and cross resistance

Answer 1

``` • soluble • administered orally • rapidly absorbed • excreted in urine Cross resistance with levamisole (if resistant to levamisole than resistant to morantel -> not the other way around) ```

Answer 2

``` paralysis by binding to GABA gated Cl-ion channels in neurons -> hyperpolarisation -> FLACCID PARALYSIS Activity: • all GINs and arthropods • NOT cestodes or trematodes • extremely potent ```

Answer 3

Depending on route different phase Oral -> High availability at GIT sites of parasites - improve therapeutic response to nematodes Subcutaneous -> high systemic availability - Extended persistence Pour-on -> large skin depot, erratic percutaneous absorption, oral ingestion (cattle -> lick other animals) - Large inter-animal variability in exposure and therapeutic response

Answer 4

Safety index: 20X - wide margin of safety Environmental effects: - persists in faeces, kills arthropods - antibacterial properties in the environment - moxidectin has less effect on dung beetles - more recent environmentally safer

Answer 5

- Naphthalophos, dichlorovos Mode of action: • inhibits acetylcholinesterase – spastic paralysis Activity: • highly effective against Haemonchus • higher doses needed to kill Trichostrongylus, Ostertagia • erratic against Nematodirus, Chabertia & Oesophagostomum Use: • used only in sheep

Answer 6

- Piperazine (diethylene diamine) Mode of action: • agonist of GABA receptors - flaccid paralysis • relies on peristaltic action to remove worms Activity: • narrow spectrum - ascarids and nodular worms (number one choice for ascarids) • given orally

Answer 7

``` - Closantel Mode of action: • uncouples oxidative phosphorylation -> deprive them of energy Pharmakokinetics: • soluble, given orally • persists for 4-6 weeks Activity: • inactive against most nematodes • cannot penetrate cuticle • highly effective against blood feeders - Haemonchus Safety index - 5x (low) ```

Answer 8

Mode of action: • causes flaccid paralysis by binding to the latrophilin receptors in parasitic nematodes Activity: • effective against most nematodes Use: • currently used in product for dogs and cats - not production animals at this stage

Answer 9

Monepantel Mode of action: (unique - so no cross-resistance) • a nematode-specific ACR-23 nicotinic acetylcholine receptor sub-unit only found in nematodes ○ Open Na ion channels ○ causes spastic paralysis Activity: • effective against most GINs in ruminants, except lungworms • Haemonchus Large safety index 30

Answer 10

CRAP Mode of action: • nicotinic antagonist causing flaccid paralysis - does not kill nematodes

Answer 11

1. Fenbendazole @ 10mg/kg/day for 5 days | 2. Moxidectin @ 0.4 mg/kg - one dose only

Answer 12

Pups • treatment every 2 weeks prior to weaning • treatment every 4 weeks after weaning • treatment every 3 months after 6 months of age (depending on risk factors -> if low risk up to 6 months) Pregnant bitches (parasites within mammary tissue) • Fenbendazole @ 50 mg/kg/day (almost 10 times normal dose) from 3 weeks prepartum to 2-15 days postpartum ○ Once infected with this larvae generally infected for life - act as a source of the parasites to the pups

Answer 13

* “single” resistance - to one class of drugs * “double” resistance - when two different parasites develop resistance to different types of anthelmintics * “multiple” resistance - one parasite developed resistance to more than one anthelmintic * “side” or "cross" resistance - if worm population developed resistance to one drug within a class (resistance is then given to other drugs in the same class OR cross resistance between classes (one class gives you resistance to another class)

Answer 14

1) Polymorphism in nematode population 2) initial frequency of resistance alleles 3) number of genes involved - one gene shorter lag phase 4) fecundity & length of life cycle -> high shorter lag phase 5) resistance genes dominant or recessive - dominant shorter lag phase 6) treatment frequency -> MOST COMMON need to use epidemiology 7) Refugia - leave 20% pop susceptible less selection longer lag phase 8) Pharmacokinetic profile of drug (“tail selection”) -> animals exposed to sub-therapeutic levels of the drug and therefore shorter lag phase

Answer 15

1) Reduced drug uptake inside the worm 2) Increased drug efflux -> P-gps (p-glycoproteins) -> transport drugs out of the cells - Possible ML (macrocyclic lactones) 3) Detoxification (get inside but metabolised rapidly) - Involves enzymes cytochrome P450 4) Altered target within the worm - Possible Lev, BZ, ADD

Answer 16

Have only 5 drug groups 1. BZ’s 2. LEV (Levamisole- Imidazothiazoles 3. OP’s 4. ML’s 5. (closantel) - Amino-acetonitrile derivatives (AAD’s) SHEEP - most issue, most with low level of resistance which isn't evident clinically

Answer 17

Trying to block P-gps that increase the efflux of drugs out of the worm - When use in vitro results in increase efficacy of the drug - Not done in animals so aren't there yet REVERSAL OF ANTHELIMITC RESISTANCE

Answer 18

1) egg hatching inhibition using benzimidazoles - count number hatch after exposure 2) tubulin binding assay using benzimidazoles 3) Larval paralysis test using Levamisole/ML - if killed won't pass through mesh 4) larval development test - Drnchrite test - eggs extracted from faeces and if hatch resistant 5) field test (faecal egg count reduction test - Anthelminitics should reduce FEC to 0 -> resistant is less than 95% reduction

Answer 19

1) check timing and administration of drenches 2) check management practice (pasture, timing) 3) double dose - NOT BZ as decrease lag time 4) Use of rotation and mixtures 5) quarantine drenches for all introduced sheep 6) use monepantel - caution don't want to get resistance here