Anthelminthics

Question 1

What does the MDR1 resistance gene code for and what drugs are affected by it?

Answer 1

P-glycoprotein which is an integral part of the BBB and is involved in active drug elimination in the liver and kidney and limits drug absorption in the gut

Question 2

What breeds are most susceptible to MDR1 mutation?

Answer 2

Australian Shepherds, Border Collies, Shelties, Old English Sheep dogs

Question 3

Breeds that have the MDR1 mutation should not be administered which drugs?

Answer 3

Macrocyclic lactones, vinca alkaloids, loperamide, paclitaxel, doxorubicin, cyclosporine, digoxin, diltiazem, losartan, morphine, butorphanol, fentanyl, steroids, erythromycin, rifampicin, ketoconazole, levofloxacin, cimetidine, acepromazine, amitryptiline, and domperidone

Question 4

Macrocytic lactones

Answer 4

MOA: Macrocyclic lactones bind to glutamate receptors that trigger chloride influx, which hyperpolarizes the parasite neuron and prevents initiation or propagation of normal action potentials. The net effect is paralysis and death of the target parasite

Helminth activity: Only has an effect against adult GI worms, only on microfilaria of filarial worms

Formulations: Ivermectin, Eprinomectin, Moxidectin, Milbemycin, Selamectin

Fun facts: excreted in the feces unchanged; Half-life of ivermectin is 2 days, moxidectin is 19 days

Adverse effects: MDR1 mutation in certain breeds, common clinical signs: vomiting, ataxia, lethargy, tachycardia, hypersalivation, mydriasis, and seizures

Question 5

Doramectin

Answer 5

Origin: Macrocytic lactone from the fermentation of Streptomyces avermitlis

Half-life: 4 days

MOA: bind to glutamate receptors that trigger chloride influx, which hyperpolarizes the parasite neuron and prevents initiation or propagation of normal action potentials

Activity:

• Cattle: GI roundworms, lungworms, eyeworms, grub, sucking lice, mange mites Injectable); pour-on can eliminate biting lice; extra-label: screwworms
• Swine: injectable- GI roundworms, lungworms, kidney worms, sucking lice, mange mites
• Dogs/cats: Off label for demodex

Adverse effects: Cattle: do not use 35-45 days from slaughter; swine do not use 24 days from slaughter

Examples: Dectomax

Question 6

Eprinomectin

Answer 6

Origin: 2nd gen Macrocytic lactone from a fermentation product of Streptomyces avermitilis

MOA: bind to glutamate receptors that trigger chloride influx, which hyperpolarizes the parasite neuron and prevents initiation or propagation of normal action potentials

Activity:

• Cattle: Pour on- barber pole worms, brown stomach worms, small intestinal worms, bankrupt worms, Nematodirus, nodular worms, hookworms (Bunostomum phlebotomum) threadworms, lungworms, and whipworms. cattle grubs, sucking lice, biting lice, mange mites, horn flies. Injectable can inhibit some of the L4
• Sheep: Pour on- GI nematode, lungworms
• Donkey: Pour-on- Strongyles
• Rabbits: Extra label for ear mites (Psoroptes caniculi
• Cats: combined with praziqunatel

Adverse effects: Do not slaughter with 45 days of inj (cattle)

Examples: Eprinex (pour on), Longrange (inj.), Centragard (cats)

No withdrawal time in meat or milk with pour on

Question 7

Ivermectin

Answer 7

Origin: Macrocytic lactone

MOA: bind to glutamate receptors that trigger chloride influx, which hyperpolarizes the parasite neuron and prevents initiation or propagation of normal action potentials.

Activity:

• Horse: large and small strongyles, pinworms, ascarid, large mouth stomach worms, bots, lungworms, threadworms, Habronema and Drashia larvae, and Oncocerca microfilariae
• Cattle: Inj.- GI roundworms, cattle grubs, lungworms, sucking lice, mange mites. Sq- prevents Dictocaulus, Oesophagostomum, common GI parasites. Off label: Parafilara bovicola and Thelazia rhosesi
• American bison and reindeer: FDA approved for grubs, and warbles (Hypoderma tarandi-Reindeer)
• Sheep: Drench-Adult and L4 H. contortus and adults only of H. placei. Stomach and GI intestinal worms, lungworms, nasal bots
• Goats: Intestinal parasites, extra label- sarcoptes
• Swine: Inj.-Adults and L4 of Ascaris suum, red stomach worms, nodular worms, threadworms, somatic larvae of Strongyloides, adult lungworms, sucking lice, mange mites. Extralabel- kidney worm
• Dogs: HW L3 & L4, ascarids, hookworms, threadworms; extra-label- demodex, sarcoptes, Cheletiella, Capillaria, eucoleus, Pneumonyssoides cannum (nasal mites)
• Cats: Ear mites, HWP, hookworms, roundworms. Extralabel- Aleurostrongylus abstrusus

Examples: Ivomec, Eqvalan paste, Heartgard

Question 8

Milbemycin oxime

Answer 8

Origin: Macrocytic lactone that is a fermentation product of Streptomyces hygroscopicus subspp. aureolacrimosis

MOA: bind to glutamate receptors that trigger chloride influx, which hyperpolarizes the parasite neuron and prevents initiation or propagation of normal action potentials.

Activity:

• Dogs: Kills L3 and L4 HW and inhibit the release of L1, hookworms, roundworms, whipworms. Extralabel- resistant demodex, sarcoptes, nasal mites
• Cats: L3/L4 HW and ear mites, hookworms and roundworms
• Turtle: Extra label uses

Formulations:

Adverse effects:

Examples:

Question 9

Moxidectin

Answer 9

Origin: Macrocytic lactone

MOA: bind to glutamate receptors that trigger chloride influx, which hyperpolarizes the parasite neuron and prevents initiation or propagation of normal action potentials.

Activity:

• Horses: larval and adult of large strongyles, adults and encysted of small strongyles, ascarids, pinworms, hairworms, stomach worms, botfly larvae
• Cattle: Gi roundworms, lungworms, mange mite (Psroptes), sucking lice
• Sheep and Goats: Gi rounds, extra-label inj. for lungworms
• Dogs: HW (L3/L4) and GI nematodes

Adverse effects: do not use in heavily parasitized thin horses, cattle under 8 weeks or lactating dairy

Examples: Quest, Cydectin

Pour on doe s not have a withdrawal time

Question 10

Selemectin

Answer 10

Origin: Macrocytic lactone, modification of doramectin

MOA: bind to glutamate receptors that trigger chloride influx, which hyperpolarizes the parasite neuron and prevents initiation or propagation of normal action potentials.

Activity:

• Dogs and cats: HWP (L3/L4), fleas, ear mites, Sarcoptes, Dermacentor variables, feline hookworms, and roundworms. Europe- labeled for Lice. Extralabel for lungworms, canine nasal mites, cats with chiggers

Adverse effects: Can be used with MDR1 dogs

Examples: Revolution

Question 11

Albendazole (helminths)

Answer 11

Origin: Benzimidazole

MOA: bind to tubulin molecules; this inhibits the formation of microtubules and disrupts cell division and may inhibit fumarate reductase which blocks mitochondrial function

Activity:

• Cattle: Oral- H. contortus and placei (larva and adults), brown stomach worm, small stomach worms, bankrupt worms, thread-necked worms intestinal worms, Cooperia, hookworms, nodular worms, tapeworms, and adult liver flukes (F. hepatica)
• Goats and sheep: F. hepatica (adults), tapeworms, fringed tapeworms (Thysanosoma actinoides), brown stomach worms, barber pole worms, small stomach worms, Cooper’s worms, bankrupt worms, nodular worms, large-mouth bowel worms (Chabertia ovina), and lung worms. Extra-label- Dicrocoelium dendriticum, lungworm
• Dogs/cats- NOT approved. Etxtra label for F. hirthi, Pearsonema plica, Paragonimus kellicoti

Adverse effects: Cannot be used in pregnant or lactating animals; 27 day withdrawal cattle, 7 days small ruminants. Aplastic anemia in dogs/cats

Examples: Zentel

Question 12

Febantel

Answer 12

Origin: Benzimidazole prodrug (metabolized to fenbendazole and oxyfendazole

MOA: bind to tubulin molecules; this inhibits the formation of microtubules and disrupts cell division and may inhibit fumarate reductase which blocks mitochondrial function

Formulations: Always a combo drug

Question 13

Fenbendazole (helminth)

Answer 13

Origin: Benzimidazole; metabolized to oxfendazole sulfoxide and oxfendazole sulfone

MOA: bind to tubulin molecules; this inhibits the formation of microtubules and disrupts cell division and may inhibit fumarate reductase which blocks mitochondrial function

Activity: Drug of choice for Giardia in pregnant animals

• Cattle: Lungworms, stomach worms, intestinal worms; In beef can increase the dose to cover tapeworms and inhibit L4 of Ostertagia
• Horses: Large strongyles, small strongyles, higher doses- ascarids, and L4 S. vulgaris (off label)
• Swine: Feed/water additive- lungworms, GI worms, kidney worms
• Dogs: Roundworms, hookworms, whipworms, and Taenia piriformis. Extralabel- Paragonimus kellicoti
• Cats: Not approved in USA. Ascarids, hookworms, whipworms, strongyloides, and Taenia sp. Possible Aluerostrongylus, Eusolus aerophilus, C. feliscati (bladder), Paragonimus kellicoti, Eurytrema procyonis (pancreatic fluke)
• Goats: Barber pole worm, brown stomach worm,
• Sheep: Not approved in USA, but used in Europe for cestode and GI and lung nematodes
• Bighorn sheep: approved for lungworms (Protostrongylus)

Examples: Panacur or Safe-Guard

Panacur is only drug in dogs proven to prevent vertical transmission

Question 14

Oxfendazole (helminths)

Answer 14

Origin: Benzimidazole

MOA: bind to tubulin molecules; this inhibits the formation of microtubules and disrupts cell division and may inhibit fumarate reductase which blocks mitochondrial function

Activity:

• Cattle: Beef and non-lactating dairy cattle- lungworms, roundworms, tapeworms
• Dogs: Lungworms (Filaroides osleri)

Examples: Synanthic Bovine Dewormer

Question 15

Oxibendazole (helminths)

Answer 15

Origin: Benzimidazole

MOA: bind to tubulin molecules; this inhibits the formation of microtubules and disrupts cell division and may inhibit fumarate reductase which blocks mitochondrial function

Activity:

• Horses: Large and small strongyles, Ascarids, Pinworms

Adverse effects: Do not use in debilitated horses

Examples: Anthelcide EQ,

Question 16

Thiabendazole

Answer 16

Origin: Original benzimidazole

MOA: bind to tubulin molecules; this inhibits the formation of microtubules and disrupts cell division and may inhibit fumarate reductase which blocks mitochondrial function

Activity:

• Cats/ Dogs for ear mites

Examples: Tresaderm

Question 17

Levamisole

Answer 17

Origin: Imidazothiazole

MOA: Nicotinic agonists that disturb the neuromuscular junctions leading to spastic paralysis and interfere with the fumarate reduction system disrupting mitochondrial energy production

Examples: Drench in sheep/cattle and soluble for pigs–> discontinued

Question 18

Pyrantel

Answer 18

Origin: Tetrahydropyrimidines

MOA: nicotinic agonists that disturb the neuromuscular junction, thus causing depolarization of the muscle membrane, contraction and subsequent spastic paralysis so they are dislodged from the normal location and interfere with fumerate reductase

Formulations:

• Pyrantel tartate- well absorbed in the pigs, rats, and dogs (not ruminants. Excreted in urine by dogs.
• Pyrantel pamoate- poorly absorbed in GI tract and excreted in feces

Activity:

• Dogs: Ascarids, hookworms,. Extralabel- Physaloptera
• Horses:
  
  • Tartate- adult and larval large strongyles, small strongyle larva, pinworms, and ascarids
  • Pamoate- adult large and small strongyles, pinworms, ascarids, tapeworms (extralabel)
• Swine: (tartate) Ascarids, prevention of Oesophagostomum, prevent the appearance of milk spots.
• Cattle, sheep, goats: Not approved but off label effective against common GI nematodes

Cannot use with piperazine (antagonist), or with levamisole or morantel

Examples: Nemex, Strongyid C, Strongid- T, Banminth 48

Question 19

Morantel tartate

Answer 19

Origin: Tetrahydropyrimidines

MOA: nicotinic agonists that disturb the neuromuscular junction, thus causing depolarization of the muscle membrane, contraction and subsequent spastic paralysis so they are dislodged from the normal location and interfere with fumerate reductase

Activity:

• Cattle: stomach worms, small intestinal nematodes, late intestinal worms (Oesophagostomum)
• Goats: Haemonchus contortus, brown stomach worms,

Adverse effects: increased respiratory rate, profuse sweating, ataxia, and other cholinergic effects. Do not use in feeds containing bentonite

Withdrawl: No mild withdrawal and 14 days for slaughter in cattle. Goat- no slaughter for 30 days, no milk withdrawl

Examples: Rumatel 88

Question 20

Emodepiside

Answer 20

Origin: Cyclic depsipeptides

MOA: direct irreversible opening of Slo-1 potassium channel. Once opened, the constant efflux of potassium leads to hyperpolarization of the membrane and subsequent paralysis of the parasite pharynx and body wall

Activity: Active against resistant nematode in sheep and cattle. Combo product in cats

Question 21

Piperazine

Answer 21

Origin: Piperazine (own class)

MOA: GABA agonist to produce a neuromuscular blockade

Activity: Limited to ascarids

• Dog/Cats: T. canis, T. cati, and T. leonina
• Pigs: Ascaris suum and Oesophagostomum
• Chicken/turkeys: Works on Ascaridid, but not Heterakis

Adverse effects: Never use in animals with compromised liver and kidneys

Examples: Pig Swig

Question 22

Praziquantel

Answer 22

Origin: Isoquinolones

MOA: exact mechanism unknown but increases cell membrane permeability to Ca++ and the resulting loss of intracellular calcium, followed by contraction of the parasite. Last it vacuolized the tegument

Activity:

• Dog/Cat: Labelled for virtually all cestode. Extralabel: Paragonimus kellicoti, Alaria
• Sheep goats: tapeworms
• Horses: Combo product, approved for A. perfoliata

Adverse effects: Gi upset in small animals

Examples: Droncit

Question 23

Epsiprantel

Answer 23

Origin: Isoquinolones

MOA: exact mechanism unknown but increases cell membrane permeability to Ca++ and the resulting loss of intracellular calcium, followed by contraction of the parasite. Last it vacuolized the tegument

Activity: low bioavailability when orally administered

• Dogs/Cats: Tapeworms; T. hydatigena, Echinococcus is extra label

Adverse effects:

Examples: Cestex

Question 24

Melarsomine

Answer 24

Origin: arsenical

MOA: unknown by thought to be impaired glycolysis

Activity:

• HW adulticide in dogs only

Adverse effects: Containdicated with caval syndrome

Examples: Immiticide and Diroban

Antedote: Dimercaprol

Question 25

Clorsulon

Answer 25

Origin: benzene sulfonamide compound but cannot be used as a sole agent (w/ ivermectin) MOA: It blocks the glycolytic enzymes 3-phosphoglycerate kinase and phosphoglyceromutase Activity: f. Hepatica immature and mature flukes, not effective against rumen flukes

Question 26

Hygromycin B

Answer 26

Origin: antibiotic produced by Streptomyces hygroscopicus MOA: inhibiting protein synthesis Activity: * Chickens: Ascaris galli, Heterakis gallinae, capillary worms * Pigs: Oesophagostomum, Ascaris suum, whipworm Adverse effects: PIgs-hearing and vision impairment Examples: Hygromix in swine and poultry