Anti-Nematode Agents Flashcards Preview

Pharm FINAL > Anti-Nematode Agents > Flashcards

Flashcards in Anti-Nematode Agents Deck (58):
1

******What are the indications for use of Levamisole in cattle, sheep and goats?
(Anti-nematode/roundworms)

FDA approved*
Cattle beef and non-lactating dairy. Sheep and goats.
-Mature and larval lung worms
-Mature stages of GI worms including Trichostrongylus.

(Swine?)

2

What are the indications for use of Levamisole in swine?
(Anti-nematode/roundworms)

Mature stages of GI worms.

3

********What are the indications for use of Levamisole is NOT indicated for use in what species?
(Anti-nematode/roundworms)

Horses, dogs and cats.

4

Levamisole
L-Tetramisole

Levamisole
L-Tetramisole has anti-nematodal effects and has toxicity.

5

Levamisole
dl-Tetramisole

Parent compound
A racemic mixture of l-tetramisole and d-tetramisole.

6

Levamisole
D-Tetramisole

Levamisole
D-Tetramisole (dud)
-Has no anti-nematodal effects and HAS toxicity.

7

********Levamisole
Pharmacodynamics:

Levamisole is a nicotinic receptor agonist.
Stimulation of nicotinic receptors in worm muscles causes tetanic paralysis***
Worms are unable to maintain attachment in the host.
*Not effective against nematode eggs, it works on the nervous system*
******ADULT GI worms are excreted in the feces paralyzed but alive! *Secondary requirements for cleaning the environment!
Similar drug to nicotine, excitatory, therefore TETANIC paralysis.

8

Stimulation of nicotinic receptors in worm muscles causes tetanic paralysis***
Worms are unable to maintain attachment in the host.
ADULT GI worms are excreted in the feces paralyzed but alive!
Drug?

Levamisole
*Similar structure to nicotine!

9

Levamisole
Absorption:

Well absorbed following oral, topical or SC administration.
SC > Oral > Topical

10

Levamisole
Distribution:

WIDELY distributed
Found in all tissues
Enters the milk of cattle within 1 hour following SC administration.

11

Levamisole
Metabolism

Levamisole is rapidly metabolized in the liver.

12

Levamisole
Elimination

90% within 24 hours (t1/2 4-6 hours in cows and pigs)
5-10% is excreted unchanged in the urine and feces
60% of metabolites are eliminated in the urine.
30% in the feces.

13

Levamisole
Adverse effects/toxicity

Stimulates nicotinic receptors in the host BUT toxicity may be from muscarinic effects due to cholinesterase inhibition (similar to organophosphate toxicity).
Signs may be apparent as low as 2xED50, but LD50 ~2-6xED50.
-Toxicity may be increased by concurrent treatment with pyrantel, morantel or cholinesterase inhibitors.
-SC administration is more dangerous then PO
-Species notes:
--Dogs are more tolerant than ruminants and pigs with PO administration.
--horses are very intolerant

14

What anti-nematode agent do you not want to administer to a patient with Mysenthia Gravis?

Levamisole
-Toxicity may be increased by concurrent treatment with pyrantel, morantel or *cholinesterase inhibitors*.

15

What anti-nematode agent that causes tetanic paralysis of roundworms, is very intolerant to horses?

Levamisole

16

Best administration route of Levamisole in dogs?

PO

17

Tetrahydropyridine drugs?

-Pyrantel pamoate/tartrate includes...
Nemex 2 (suspension)
Strongid (paste)
Strongid T (suspension)
and
Morantel tartrate

*Both drugs are available OTC

18

What are the indications for use of
Tetrahydropyridine; Morantel tartrate?

GI worms in cows, sheep and goats.

19

******What are the indications for use of
Tetrahydropyridine; Pyrantel pamoate/tartrate
Nemex 2 (suspension)
Strongid (paste)
Strongid T (suspension)

GI worms in swine, horses (large and small strongyles) dogs and cats.

20

********What are the pharmacodynamics of Tetrahydropyridine drugs?
Pyrantel pamoate/tartrate includes...
Nemex 2 (suspension)
Strongid (paste)
Strongid T (suspension)
and
Morantel tartrate

Same as levamisole
Nicotinic receptor agonist.
Stimulation of nicotinic receptors in worm muscles causes tetanic paralysis***
Worms are unable to maintain attachment in the host.
*Not effective against nematode eggs, it works on the nervous system*
ADULT GI worms are excreted in the feces paralyzed but alive!
Similar drug to nicotine, excitatory, therefore TETANIC paralysis.

21

*********Never give what drug with Levamisole?

**Tetrahydropyridine drugs**
Pyrantel pamoate/tartrate includes...
Nemex 2 (suspension)
Strongid (paste)
Strongid T (suspension)
and
Morantel tartrate

22

Tetrahydropyridine drugs:
Pyrantel pamoate/tartrate includes...
Nemex 2 (suspension)
Strongid (paste)
Strongid T (suspension)
and
Morantel tartrate
Absorption:

Poor (morantel is worse then pyrantel) ONLY administered PO.
Maintained in the GI tract of ruminants for up to 98 days.
Better absorption when given with food in small animals due to a slower GI transit time.

23

Tetrahydropyridine drugs:
Pyrantel pamoate/tartrate includes...
Nemex 2 (suspension)
Strongid (paste)
Strongid T (suspension)
and
Morantel tartrate
Distribution not to the..

NOT distributed to the milk.

24

Tetrahydropyridine drugs:
Pyrantel pamoate/tartrate includes...
Nemex 2 (suspension)
Strongid (paste)
Strongid T (suspension)
and
Morantel tartrate
Elimination

40% is eliminated in the urine so beware of patient renal status!

25

Tetrahydropyridine drugs:
Pyrantel pamoate/tartrate includes...
Nemex 2 (suspension)
Strongid (paste)
Strongid T (suspension)
and
Morantel tartrate
Adverse effects?

None seen at treatment doses: LD50 7xED50 (pyrantel) and 210xEDxED50 (morantel)
Horses tend to tolerate the tartrate salt better then the pamoate salt.

26

Piperazines formulations?

RX and OTC

27

*****Piperazines
Indications in dogs and cats:

Dogs and Cats: Toxocara and Toxascaris leonine.

28

******Piperazines
Indications in horses:

Cyanthomes, ascarids and pinworms (rarely used)

29

*******Piperazines
Indications for use in pigs:

Ascarids and nodular worms

*NOT CATTLE

30

*********Piperazines
Pharmacodynamics

GABA receptor agonist: shuts down nervous system.
-hyperpolarizes muscle cells, makes them less responsive to signaling through nicotinic acetylcholine receptors, causes FLACID paralysis of worm muscles.
*********Not effective against nematode eggs, it works on the nervous system*

31

*********Because Piperazines cause FLACID paralysis, this drug will compete with what two drugs?

Levamisole and Tetrahydropyridines

32

Piperazines
Pharmacokinetics

Well distributed following PO administration (strong base)
Distributes into most tissues except fat
Metabolized by the liver
Eliminated in the urine.

33

*********Piperazines
Adverse effects:

Few at recommended doses.
Dogs and cats (at large doses): emesis, diarrhea, ataxia, muscle tremors, behavior alterations, and head pressing).
Horses: no effects at 6 to 7 times the treatment dose.

34

**********What is Diethylcarbamazine citrate?
NOT AN ANSWER ON THE EXAM

Withdraw from the market by manufacturer.
******Used as a heartworm (d. immitis) preventative in dogs.
******Inhibits the production of PGE2 and PGI1, which the worms use to able themselves to live in the host circulation without causing clotting.
Requires DAILY dosing throughout mosquito season.
Can ONLY be used against larval stages; anaphylactic shock can result from threating the adult filariae.
NOT AN ANSWER ON THE EXAM

35

*************Emodepside is in what drug?

In PROFENDER with Praziquantal.

36

***********What are the indications for use of Emodepside?

Labeled for use of toxocara cat and Ancylostoma tubaeforme in cats*

37

***********Emodepside
Pharamcodynamics:

Latrophilin receptor agonist in nerves
-Induces the release of PF1-like neuropeptides in the synaptic cleft, which *hyperpolarizes* the muscle cells in the nematode pharynx. Causes FLACCID paralysis of muscles needed for ingestion.

38

***********This drug induces the release of PF1-like neuropeptides in the synaptic cleft, which *hyperpolarizes* the muscle cells in the nematode pharynx. Causes FLACCID paralysis of muscles needed for ingestion.

Emodepside

39

Emodepside pharmacokinetics?

Absorbed within 2 hours and reaching maximum circulating levels within 6 hours.
Detectable in plasma for up to 28 days following administration.

40

Emodepside
Adverse effects:

Generally well tolerated, with minor, self-limiting effects in 3% or fewer cats.

41

***********What is Melarsomine?

Immiticide
Arcinine (with an arscenic molecule).
**********Indicated for d. immitis in dogs over 5 months in stable stage I, II or III disease. (Fully reproductive adult worms)******
Labeled for use in HOSPITAL setting only!

42

What anti-nematode agent is labeled to be used ONLY in a hospital setting?

Melarsomine

43

Melarsomine
Pharmacodynamics and Pharamcokinetics?

PD unknown.
PK (dogs)
Rapidly absorbed after IM injection, metabolism not known, t1/2 is 3 hours.

44

***********Melarsomine is used for what stages of heartworm disease?

Indicated for d. immitis in dogs over 5 months in stable stage I, II or III disease.

45

Indicated for d. immitis in dogs over 5 months in stable stage I, II or III disease.

Melarsomine

46

*************Melarsomine
Adverse effects?

VERY toxic in cats!
Dogs:
********Injection site inflammation (weeks to resolve)******** 30% of patients*******
plus coughing, gagging, lethargy, inappetence, fever, lung congestion, vomiting, paresis/paralysis.
Increased risk when administering IV and SC

47

********Resistance has been observed in ALL classes of what anti-helminth drug group?

Anti-nematode agents.
*Resistance to one member of a drug class, tends to cause resistance to all members of a drug class.
All mechanisms involving altered genetics are heritable.
Reversion/loss of resistance has NOT been observed in parasites.

48

********Some strains of H. contortus have reduced expression of nicotinic acetylcholine receptors, causing resistance to..

Levamisole and tetrahydropyridine drugs (pyrantel and morantel)*********

*Resistance generated in one drug, lead to resistance in another.
Mechanism of resistance? Changes in the number of target enzymes in parasite (transcriptional or translational) for the drug

49

*********Some strains of H. contortus have altered their B-tubulin structure which makes them resistant to..

Benzimidazoles (Albendazole, Fenbendazole and thibendazole).
Mechanism of resistance? Changes of structure and affinity of target enzymes for the drugs.

50

*********Some strains of H. contortus have increased expression of P-gp making them resistant to

Benzimidazoles (Albendazole, Fenbendazole and thibendazole)
And Avermectins (macrocyclic lactones)
Mechanism of resistance?
Modification of parasitic enzyme systems causing reduced drug accumulation.

Also anti-cancer drugs.

51

What are treatment recommendations for using anti-helminth drugs?

-Use drugs for the indicated species treating; get comprehensive lists of susceptible worms from the manufacturers, stay up to date on which nematodes are susceptible to which agents.
-Give the full treatment course (usually 2 treatments)
-Rotate between indicated drugs (after one course of one drug, consider a new one next season)
-Treat at defined thresholds; plan with owners and treat at pre-arranged burdens.
-Monitor the parasite levels in patient populations and herds. This is the only way to assess response to treatment.

52

Low continuous levels of an anti-parasite drug tends to...

PROMOTE RESISTANCE.

53

How do you monitor the success of anti-helminth treatment?

Monitor the parasite levels in patient populations and herds.

54

What two drugs are considered Benzimidazole?

Albendazole and Fenbendazole

55

What drugs are considered tetrahydropyridines?

Pyrantel Pamoate, pyrantel tartrate, and morantel tartrate.

56

What drugs are considered piperazines?

Piperazine and diethylcarbamazine

57

Benzimidazole work by..

Inhibiting microtubule polymerization****
Specific to microtubule formation in worms.
Anti-nematode agent- dissociates from the parasite tubulin more slowly, effective against an anti-nematode agent. Not an effective neoplastic agent.

58

Anti-neoplastic drugs that at on micro tubulin formation in humans (as appose to benzimidazole)..

Longer occupancy times on the mammalian tubulins
This makes them effective anti-cancer drugs.