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.pharmocology > Protein Synthesis Inhibitors (ribosomes > Flashcards

Protein Synthesis Inhibitors (ribosomes Flashcards

1
Q

Aminoglycosides

A

Gram- aerobes (pseudomonas, best drug)
Selected gram + aerobes (staph)
Combination therapy (with B-L)
Nocardia and atypical mycobacteria

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2
Q

Aminoglycosides structure- activity relationship

A

Weak base
Oxygen dependent
Resistance to obligate anaerobes

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3
Q

Aminoglycosides PK

A

Initiation of protein synthesis (bactericidal)
Concentration dependent (10x MIC)
Long post abx effect (once daily dosing)

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4
Q

How does pH affect aminoglycosides

A

Alkaline pH → enhanced efficacy
Acidic pH → trapped → ↓ oral absorption, milk and enhances renal toxicity

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5
Q

How do aminoglycosides interact with organs/ tissues

A

Water soluble, poorly lipid soluble
Limited passive diffusion through membranes
Poor distribution intracellularly, CNS and eye
Selectively binds to kidney, cochlea and vestibular apparatus (80-100 yrs t 1/2)

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6
Q

Aminoglycosides adverse effects

A

Toxicity dose related
Acute tubular nephrosis
Risk based on # of amines (+ charges)
Toxicity for cochlea and vestibular apparatus

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7
Q

Aminoglycoside neurologic effect

A

Neuromuscular paralysis (antagonized with neostigme or calcium)
Interferers with calcium flux and ACh release

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8
Q

How do Aminoglycosides affect cells in the cochlea and vestibular apparatus

A

Destroys sensory cells, irreversible damage
Ataxia, loss of balance, vertigo, high frequency hearing loss

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9
Q

Aminoglycosides compliance

A

ELDU discouraged but not prohibited

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10
Q

Approved aminoglycosides for food animals

A

Apramycin
Gram - infections
Pig and calves 28 day withdrawal

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11
Q

Gentamicin

A

Broad-spectrum, used with B-L, synergistic effects
Used for infections requiring aminoglycosides

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12
Q

Amikacin

A

Intrauterine for horses
Broad spectrum effective against ESBL producing E. coli

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13
Q

What is Amikacin used for?

A

Infections caused by E. coli, Klebsiella, pneumoniae and other multi-drug resistance bacteria

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14
Q

Apramycin use

A

In pigs for colibacilosis (pig scours)

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15
Q

Neomycin

A

Mostly topical or oral use
Local effect in the intestine
Treats enteritis caused by E. coli

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16
Q

Aminoglycosides resistance

A

Inherent: Obligate anaerobes and facultative anaerobes
Acquired: enzymatic destruction

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17
Q

Tetracyclines

A

Broad spectrum, safe to use, frequent cross resistance
Batceriostatic

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18
Q

Tetracyclines MOA

A

Prevents aa tRNA binding that blocks protein synthesis
Mammalian protein synthesis inhibited @ high concentrations

19
Q

Tetracyclines PK

A

90-100% and broad for doxycycline (GI and eye)
Absorption ↓ by food
Wide distribution to body fluids and tissue, not CNS

20
Q

Tetracycline binds to ________

A

Calcium

21
Q

Tetracycline therapeutic uses

A

Broad spectrum G+ and G- aerobes and anaerobes
Rickettsia, chlamydia, ehrlichia and mycoplasma (doxycycline)
Anaplasmosis: oxytetracycline

22
Q

______ are growth promotors in cattle and swine

A

Tetracyclines (in certain countries)

23
Q

Tetracyclines adverse effects

A

Brown discoloration of the teeth
Doxycycline: nausea, vomiting, esophageal erosin in cats
Disruption of ruminal flora
Collapse with IV prep (cardio depression)

24
Q

Tetracylines mechanism of resistance

A

Efflux pumps: ↓ accumulation via plasmid-bone transporter that pumps the drug out of bacteria
↓ binding to ribos
Enzymatic inactivation

25
Q

Phenicols PK

A

Good oral absorptions
Inhibits microsomal enzymes

26
Q

Phenicols MOA

A

Binds irreversibly to 50S ribosomal subunit and blocks peptidyl transferase → inhibits tranpeptidation and protein synthesis

27
Q

Phenicols

A

Broad spectrum, obligate anaerobic
Eye, ear, mammary gland
Systemic infections caused by G- bacteria

28
Q

__________ are an alternative to tetraclycines against rickettsia, chlamydia, ehrlichia

A

Phenicols

29
Q

Chloramphenicol: ADR

A

Causes irreversible aplastic pancytopenia
Banned in food animals
Potent inhibitor of hepatic drug metabolizing enzymes

30
Q

Florfenicol

A

Used for resp. diseases in cattle (shipping fever, infectious pododermatitis), swine (pasteurella, haemophilus, cornybacterium)

31
Q

Clindamycin

A

Bacteriostatic, accumulation in WBC
Gram+ aerobes (Staph and strept), anaerobic, actinomycetes

32
Q

Adverse drug events of clindamycin

A

Disruption of GI microflora (pseudomembranous enterocolitis, horses)

32
Q

Macrolides

A

Broad, excellent Gram +, lipid soluble, acid labile drugs

33
Q

Macrolide drugs

A

Erythromycin, azithromycin
Tylosin and Tilmicosin for animal use only

34
Q

Macrolides MOA

A

Accumulates G+ 100 fold compared to G-
Blocks the transfer of growing polypeptide from the A site to the P

35
Q

Tilmicosin uses

A

Bovine resp. disease (single treatment)

36
Q

Tilmicosin adverse effects

A

Lethal to swine, goats, rabbits and humans
GI: fatal to horses

37
Q

Where is tilmicosin prohibited in

A

Dairy cattle, veal calves

38
Q

Streptogramines

A

Similar action as erythromycin with prolonged postabx affect
G+ cocci and vancomycin-resistant Enterococcus faecium

39
Q

Adverse effects of streptogramines

A

Inhibits CYP3A4

39
Q

Tiamulin

A

Growth promotor in swine
Used against swine dysentery and pneumonia, porcine colonic spirochaetosis, porcine proliferative enteropathy, leptospirosis, mycoplasmosis in cattle

39
Q

Oxazolidinone (linezolid)

A

Bacteriostatic that interferes with 50s subunit and 23S ribosomal RNA
G+ and vancomycin resistant enterococcus faecium
Advers: thrombocytopenia

39
Q

Streptinomycin

A

Bacteriostatic
Gram- infections
Feed additives daily 3-5 days
Resistance develops rapidly

.pharmocology (21 decks)

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