Lecture 34: Macrocyclic Lactones Flashcards
1
Q
are macrocyclic lactones cidal or static
A
Cidal
2
Q
Macrocyclic lactones have activity against both ___ and ___
A
Nematodes and ectoparasites
3
Q
What avermectins are for use in food animals
A
Ivermectin, eprinomectin, doramectin
4
Q
What milbemycin is approved for use in food animals
A
Moxidectin
5
Q
What avermectins are for use in small animals
A
Selamectin, ivermectin
6
Q
What milbemycins are approved for use in small animals
A
- Moxidectin- dogs only
- Milbemycin oxime
7
Q
What spinosyn is approved for use in small animals
A
Spinosyn A/D
8
Q
What avermectins is approved for use in horses
A
Ivermectin
9
Q
What milbemycin is approved for use in horses
A
Moxidectin
10
Q
Topical macrocyclic lactones are more effective against ___in ruminants
A
Biting lice
11
Q
What macrocyclic lactones are effective against horn flies in ruminants
A
Ivermectin and eprinomectin
12
Q
What does ivermectin tx in pigs
A
GI roundworms, lungworms, lice, sarcoptic mange
13
Q
What is ivermectin and Moxidectin use for in horses
A
GI roundworms
14
Q
Ivermectin in horses has better activity against ___
A
Gastrophilus intestinalis (bots)
15
Q
Moxidectin in horses has better activity against ___
A
Cyanthostomum (GI round worms)
16
Q
What is ivermectin use for in dogs
A
- Prevention of D. Immitis
- Generalized demodicosis, Cheyletiella (zoonotic), sarcoptes scabieie, otodectes, pneumonyssoides spp
17
Q
What is selamectin used for in dogs
A
- Prevention of D. Immitis
- Fleas
- Otodectes spp
- Sarcoptes scabiei
- Dermeacentor variabilis
18
Q
What is milbemycin oxime effective against in dogs
A
- D. Immitis prevention
- GI round worms
- Hookworms (zoonotic)
- Whipworms
19
Q
What is Moxidectin used for in dogs
A
- Prevention D. Immitis
- Hookworms only
20
Q
What is spinosad effective against in dogs
A
Fleas
21
Q
All macrocyclic lactones are effective against stage __ and __ larvae of D. Immitis
A
Stage 3 and 4
22
Q
What is ivermectin used for in cats
A
Prevention of D. Immitis
23
Q
What is selamectin used for in cats
A
- Prevention of D. Immitis
- Fleas
- Otodectes spp
- T. Cati
- A tubaeforme (hookworms)
24
Q
What is milbemycin oxime effective against in cats
A
- D. Immitis prevention
- GI roundworms
- Hookworms
25
What is spinosad used for in cats
Fleas (dosing is higher than in dogs)
26
What is class 1 heart worm disease on severity scale
Asymptomatic, positive antigen test
27
What is class 2 heart worm disease on severity scale
Moderate pulmonary damage, coughing, exercise intolerance
28
What is class 3 heart worm disease on severity scale
right CHF, cor pulmonale, syncope, anemia, cache is
29
What is class 4 heart worm disease on severity scale
= caval syndrome
Shock, DIC, jugular distention, mitral regurgitation
30
What classes on severity scale for heart worm disease can be treated with drugs
1-3
31
What class on severity scale of heart worm needs sx intervention
Class 4
32
What species does microfilaria rarely circulate and host is often able to mount an immune response and kill worms
Cats
33
What larval stages are macrocyclic lactones effective against
Only L3 and L4, no adults
34
What stage of heart worm, worms is melarsomine effective against
Adult females, antigen positive
35
What is the split dose tx for heart worm
1. Start on avermectin monthly
2. Reduce activity- cage rest
3. 1 month later start doxycycline
4. 1 month after that 1st melarsomine dose
5. 1 month after that 2nd and 3rd melarsomine doses 1 day apart
36
What is wolbachia
Gram - rickettsia bacteria that infects heart worms
37
What is wolbachia associated with
1. Survival of filaria
2. Production of filaria
3. Infectivity of filaria (L3)
4. Pulmonary and renal inflammation via wolbachia surface protein
38
What drug is used to target wolbachia in heart worm
Doxycycline
39
Doxycycline is given to target wolbachia 30 days prior to ___
Melarsomine
40
What is the critical role/ purpose of doxycycline
Reduces worm burden prior to adulticide so decreases risk of thrombosis and inflammatory reaction to dead worms
41
What is melarsomine labeled for
D. Immitis >5 months in dogs in stable Class 1-3 disease
42
Melarsomine can only be used in __ settings
Hospital
43
Melarsomine is absolutely contraindicated in dogs with ___
Caval syndrome
44
What are some risks associated with melarsomine
1. Pulmonary thromboembolic events
2. Hyperventilate reactions
45
Melarsomine has increased risk of adverse effects in dogs if given __ or ___
IV or SQ injections
46
What are some adverse effects of melarsomine in dogs
1. Injection site inflammation
2. Coughing/gagging
3. Lethargy
4. Inappetence
5. Fever
6. Lung congestion
7. Vomiting
8. Paresis/ paralysis
47
Melarsomine is very toxic in what species
Cats
48
What is the PD of macrocyclic lactones
1. Noncompetitive agonist of glutamate activated chloride channels—> flaccid paralysis of somatic musculature and pharyngeal pump
2. Agonist of GABA receptors found on ventral nerve cord and head of nematodes
49
Glutamate is a __ neurotransmitter in nematodes
Inhibitory
50
Macrocyclic lactones also inhibit the ___in female nematodes
Reproductive tract
51
Macrocyclic lactones are highly lipophilic drugs that are poorly absorbed in ___GI tract
Ruminant
52
Ivermectin bioavailability is __% in cattle, but __% in dogs
25-33%, 95%
53
Selamectin bioavailability is __% in dogs, but __% in cats
5%, 75%
54
Macrocyclic lactone plasma concentration is = to ____concentration and therefore effective against ___
Skin concentration
Effective against ectoparasites
55
T or F: macrocyclic lactones have a wide distribution
True
56
Macrocyclic lactones rapidly distributes to ___which serves as a depot and slows elimination
Adipose tissue
57
Macrocyclic lactones are extensively distributed to __ and ___, and permeates ___
Lung, skin, permeates BBB
58
Macrocyclic lactones are metabolized by the ___in sheep and cattle
Liver
59
Macrocyclic lactones are eliminated via
95% fecal, 5% urine
60
20% of doramectin and metabolites undergo ___recirculation in sheep
Enterohepatic
61
Avermectins are eliminated in the ___ and therefore use is restricted to ___animals
Milk, non-lactating animals
62
What avermectins are not eliminated in milk and which one can be used in lactating cows
1. Eprinomectin
2. Moxidectin- use in lactating cows
63
What is required to move macrocyclic lactones out of tissues and is therefore contraindicated in what breed
P-gp, contraindicated in collies
64
What gene is associated with P-gp
MDR1
65
Collies have what deletion resulting in MRD1 mutation
4 base pair inactivating deletion of ABCB1-1
66
What are some adverse effects of macrocyclic lactones in ABCB1-/-
Vomiting, tremors, ataxia, myriads is, blindness, seizures
67
Ivermectin is toxic at <___dose in ABCB1-/- dogs
<2x normal dose
68
What are some safer alternate macrocyclic lactones to be used in collies
1. Selamectin (6.5x normal dose)
2. Milbemycin oxime (2x normal dose)
69
Combination of ivermectin with ___increased BBB permeability and increased toxicity
Spinosad (flea tx)
70
In all species with any of the macrocyclic lactones ___reactions may occur with large worm burdens
Hypersensitivity reactions
71
What is the frontline approach to prevent hypersensitivity reactions to macrocyclic lactones due to large worm burden
Doxycycline, steroids
72
Organisms resistant to macrocyclic lactones have mutation or increased expression of ___
P-gp
73
What species has been found to be ivermectin resistant in sheep/goats
Haemochus
74
What species have been found to be ivermectin resistant in cattle
Trichostrongylus
75
What are some treatment options for ivermectin resistant strains
1. Verampil- reverses P-gp
2. Moxidectin currently retains activity
