Macrolides

Question 1

Chemistry

Answer 1

Weak bases- reach high IC cc

macrocyclic lactone ring with sugars

Question 2

Mechanism and mode of action:

Answer 2

50S- protein synthesis inhibitors,

bacteriostatic, at high cc- bactericidal- respiratory tract

Question 3

Spectrum:

Answer 3

Gram+.
Fastidious.
rickettsia, chlamydia. mycoplasma, pasteurella, mannheimia.

Question 4

Resistance:

Cross resistance:

Answer 4

Decreased permeability.
Modified binding site at 50S= don’t bind macrolides.

Cross resistance: lincosamide and phenicol due to degrading enzyme.

Question 5

Ion trapping:

Answer 5

NH2-R= lipophilic. Enters the cell and the charge becomes NH3+ -> can’t leave cell and accumulation happens.
Macrolide: 1 N
Azalide: 2 N
Triamilide: 3 N

Question 6

Spectrum:

Answer 6

Gram+: very active. similar to penicillin.

Few gram-: pasteurella, campylobacter (100% in raw chicken. dog, cat, human enteritis)

Anaerobic, fastidious

Question 7

Indication:

Answer 7

brachyspira hyodysenteriae- Tylvaosin
Lawsonia intracellularis- proliferative enteropathy in swine- Tylosin, Tylvalosin (in horse doxycycline is first choice)
Bordetella- kennel cough, atrophic rhinitis
Mycoplasma
Chlamydophila
Borrelia- lyme disease (doxycycline first choice)
Rhodococcus egui pneumoniae- long treatment! 6 wks. Azithromycin, clarithromycin, erythromycin.

Question 8

Pharmacokinetics Abs, distr.

Answer 8

Absorption: good- lipophilic. Oral usually good. Eryhromycin sensitive- need film/ capsule if oral.
NEVER IV!!! - not water soluble!
IM, SC= painful, so only in farm animals.
Tylosin phosphate= 15% oral abs= good in GI inf
Tylosin tartarate= 30% oral abs= respiratory tract inf.
Distribution: good- reach all tissues- but not BBB.
cross placenta, prostate, bone
Higher in lungs than plasma
High IC cc -> kills IC bacteria- mycoplasma, chlamydia, lawsonia, rickettsia rhodococcus equi pneumoniae

Question 9

Pharmacokinetics met, exc

Answer 9

Lipophilic, extensive metabolism in liver= don’t give to liver patients.
excreted 90% by bile, both actie and inactive -> dysbacteriosis!
DONT GIVE ADULT HORSE! or herbivore rodents.
OK in kidney patients
CYP450 enzyme inhibitor- toxicity increase.

Question 10

Foals:

Answer 10

Treat rhodococcus equi in foals. long treatment 6 wks. remove from mare- if she eats foal’s feces, she will die!

Question 11

Side effects:

Answer 11

very irritant: GI -> diarrhea, vomiting
Motilin agonist: erythromycin: good to use in delayed gastric emptying in dogs and cats.
Dysbacteriosis- FATAL to adult horse and herbivore rodents.
Tissue irritant- don’t give small animals- they are sensitive.

Question 12

Erythromycin:

Answer 12

rarely used in vet med, use in penicillin allergic humans
gram +
small animals: campylobacteriosis
food producing animals: resp tract inf., mycoplasmosis, diamond skin disease.
Horse: requi+rifampicin- 6 wks treatment (foal)

Question 13

Spiramycin

Answer 13

Mainly small animals
Reach high tissue cc. 
Gingiva that is inflammed- reach high cc
treat oral cavity inf. in small animals
small animals: stomatitis
Large animals: RARELY used, but mastitis

Question 14

Tylosin

Answer 14

frequent resistance (swine dysentery 100% resistant!)
Proliferative enteropathy- lawsonia
NOT TO HORSE!- kills!
Pigs, ruminants, poultry: clostridium perfringens- necrotic enetritis, respiratory tract
Large dogs: ARD (antibacterial response diarrhea)

Question 15

Tilmicosin

Answer 15

Ruminants, pigs, poultry
NOT GOAT!
EXTREMELY TOXIC TO OTHER ANIMALS- kills!!
Cardiac toxic
Cattle: SC
Pigs and poultry: PO
IV: Kills!
Why use if dangerous? - reach outstanding cc in lung and one dose is good for 3-4 days.
Fastidious and mycoplasma are very sensitive

Question 16

Tylvalosin

Answer 16

oral application, water soluble

outstanding against: brachyspira, lawsonia, mycoplasma, fastidious

Question 17

Tulathromycin, gamithromycin

Answer 17

large animals: ruminants and swine
excellent distribution and outstanding levels in cells and lungs. Injectable.
outstanding against: fastidious, mycoplasma
Gram- decrease
several 100x higher cc in lungs than plasma= respiratory tract inf

Question 18

Tildipirosin

Answer 18

injection.
ruminants and swine
excellent distribution.
outstanding against: fastidious but NOT mycoplasma
duration of treatment is about 1 m.
several 100x higher cc in lungs than in plasma= respiratory tract inf

Question 19

Azithromycin, clarithromycin

Answer 19

oral application, small animals and humans- tablet.
long half life. outstanding against gram+, gram-, fastidious. Borrelia, mycoplasma, campylobacter, R. equi
Good lung cc.
Very expensive drug group.
Dose:
Dogs Azithromycin: 10mg/kg SID, Clarithromycin 10mg/kg BID
SE: vomiting- always give with food!