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Pharmacology II > LEC 20 - Inhibitors of Nucleic Acid Synthesis > Flashcards

LEC 20 - Inhibitors of Nucleic Acid Synthesis Flashcards

1
Q

When is nitrofurantoin most effective?

A

Acidic urine

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2
Q

What specific organisms tend to be highly resistant to sulfa drugs? (5)

A

Ricketsia

Fungi

Molds

Mycobacterium tuberculosis

Spirochetes

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3
Q

Therapeutic Use - Sulfadimethoxine

A

Long acting

More soluble + less toxic

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4
Q

How are sulfa drugs excreted from the body?

A

renal excretion of unchanged drugs + metabolites

Via glomerular filtration + active secretion + passive tubular reaborption

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5
Q

Therapeutic use - Orbifloxacin + Marbofloxacin

A

Dermal + Respiratory + Urinary infections - dogs and cats

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6
Q

Why are sulfonamides safe for mammals?

A

Mammals require formed folic acid and do not require synthesis of it.

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7
Q

How are fluoroquinolones distributed throughout the body?

A

Wide distribution

Including CNS, bone, and prostate

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8
Q

Therapeutic use - Danofloxacin

A

Bovine respiratory infections

Mannheimia species

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9
Q

What are the sulfoamides derivitives of?

A

Beneze sulfanilamide

Produced by substitution of the amino group

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10
Q

What are the side effects of trimethoprim or ormetoprim?

A

Decrease in plasma levels of thyroid hormones

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11
Q

Why is rifampin combined with erythromycin?

A

Treatment of rhodococcus equi infections in foals

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12
Q

What are the three sulfonamide mixtures that are used?

A

Sulfadiazine + trimethoprim

Sulfamethoxazole + trimetoprim

Sulfadimethoxine + ormetoprim

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13
Q

What are the side effects seen with sulfa drugs?

A

Renal crystalluria

KCS

Hypoprothrombinemia + Thrombocytopenia

Arthritis

Reduced sperm counts

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14
Q

Therapeutic use - Orbifloxacin only

A

Gram (-) infections in horses

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15
Q

What is the specific mechanism of action for fluoroquinolones?

A

Inhibit bacterial DNA gyrase + topoisomerase enzymes that control DNA supercoiling

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16
Q

How do sulfa drugs cause renal crystalluria?

A

Precipitaion of sulfonamides in neutral or acidic urine

Occurs more often with large or prolonged doses w/ inadequate water intake

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17
Q

How is nitrofurantonin used?

A

lower urinary tract infections in dogs and cats

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18
Q

What are the three other drugs that interfere with nucleic acid synthesis but do not belong to a group?

A

Metronidaole

Rifampin

Nitrofurantoin

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19
Q

Therapeutic use - Enrofloxacin

A

Dermal + respiratory + urinary infections

in

Dogs - cats - brids

(only respiratory infections in cattle)

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20
Q

What can metronidazole be combined with? Why?

A

Clindamycin

Prevent pseudomembranous colitis

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21
Q

What protozoas does metronidazole act against?

A

Giardia

Trichomonas

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22
Q

What does enrofloxacin work for in regards to bovine respiratory disease?

A

M. haemolytica

P. Multocida

H. Somni

M. Bovis

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23
Q

How is rifampin distributed throughout the body?

A

Wide distribution to cells and tissues

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24
Q

How is rifampin excreted?

A

Primarily in the bile

up to 30% can be excreted in the urine

Parent drug can also be excreted

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25
Q

How are potentiated sulfa drugs handled in the body?

A

Widely distributed

Transcellular fluid = 80% of plasma concentration

Bind to albulmin

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26
Q

How is rifampin adminstered?

A

TID

Foals + Dogs + Cats

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27
Q

What adverse effects are seen with fluoroquinolone use?

A

Reversible erosion of articular cartilage in dogs and foals

Retinal degeneration in cats

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28
Q

What is the protocol for Enrofloxacin use in cattle?

A

Can be given for up to 5 days in cattle

Or

Single high dose for respiratory infections

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29
Q

What type of inhibtion does sulfa drugs cause with PABA?

A

Competitive

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30
Q

What are the adverse effects of rifampin?

A

Hepatotoxicity with pre-existing liver disease

Re-oranged colored urine, sweat, and saliva but not harmful

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31
Q

How two drugs can be mixed with sulfa drugs to make potentiated sulfonamides?

A

Trimethoprim

Ormetoprim

32
Q

What is the specific mechanism of rifampin?

A

Inhibits DNA-dependent RNA polymerase

Prevents initiation of RNA synthesis

33
Q

What happens with elmination rate with rifampin after repeated doses? why?

A

increased elimination

induces microsomal enzymes

34
Q

Sulfonamides (5)

A

Sulfamethazine

Sulfadimethoxine

Sulfachlorpyridazine

Sulfacetamide

Sulfasalazine

35
Q

What happens to the bacteria if folic acid is decreased?

A

Cannot multiply, grow, and survive

36
Q

How does elimination of the parent drug and metabolite differ with rifampin?

A

Parent drug is reabsorbed in the gut while the metabolite is not

37
Q

How can nitrofurantoin be adminstered?

A

Ointment

Powder

Water-soluble wound dressing

38
Q

What do potentiated sulfa drugs allow for?

A

Sequential blockade of folate synthesis

39
Q

How is sulfasalazine processed in the gut?

A

Cleaved into sulfapyridine + 5-ASA via the gut bacteria

40
Q

How are fluoroquinoles metabolized?

A

Hepatic metabolism

41
Q

Where do potentiated sulfa drugs tend to concentrate in the body?

A

Prostate, making it a good therapy for praostatitis

42
Q

What is different about sulfa drug metabolism in dogs?

A

There is no acetylation

43
Q

What type of bacteria tend to be resistant to fluoroquinolones?

A

Anaerobes

44
Q

What type of respiratory infections in cattle does danofloxacin work for?

A

M. Haemolytica

P. Multocida

45
Q

What breed of dog is most susceptible to arthritis from sulfa drugs? what is the most common drug that causes this?

A

Dobermans

Suldasalazine

46
Q

Therapeutic Use - Sulfasalazine

A

Enteric sulfa drug

Colitis + IBD in dogs and cats

47
Q

How does resistance against fluoroquinolones occur?

A

DNA gyranse

+

Topoisomerase

mutations

48
Q

How are fluoroquinolones excreted?

A

Parent drug (15 to 50%)

and metabolites excreted in bile and urine

49
Q

Why is rifampin combined with antifungal agents?

A

Treat fungal infections like aspergillous or histoplasmosis in dogs and cats with CNS infections

50
Q

Therapeutic Use - Sulfamethazine

A

Cattle + Sheep + Swine

51
Q

What so the metabolites of sulfasalazine do?

A

Sulfapyridine = antibacterial agent

5-ASA = anti-inflammatory

52
Q

How is the Rifampin metabolized?

A

Liver

Metabolite is antibacterial as well

53
Q

What is the structure of sulfasalazine?

A

Linked to a molecule of 5-ASA

54
Q

What is PABA important for?

A

Intergral part of folic acid synthesis

55
Q

What is the use of metronidazole?

A

Dogs, horse, + cats = severe infections caused by anaerobic pathogens

most importantly - brain abcesses + pelvic/genitourinary tract/respiratory infections

56
Q

When are sulfoamides bactericidial?

A

Urinary tract infections due to the fact that the drug concentrates there and reaches high enough levels

57
Q

Therapeutic Use - Sulfachlorpyridazine

A

Rapidly absorbed + excreted

Orally in Cattle under 1m

Swine - respiratory + enteric infections (colibacillosis)

58
Q

Fluoroquinolines (5)

A

Enrofloxacin

Danofloxacin

Diflozacin

Orbifloxacin

Marbofloxacin

59
Q

How is nitrofurantoin processed in the body?

A

Reduced by bacteria to reactive intermediates that inhibit nucleic acid synthesis

60
Q

What is the specific mechanism of action for metronidazole?

A

Anaerobic bacteria + protozoa takes up drug

Reduces to cytotoxic metabolite = DNA disruption

61
Q

How are potentiated sulfa drugs adminstered?

A

Orally

Injectables

62
Q

How are potentiated sulfa drugs metabolized in the body?

A

Via actylation + glucuronide conjugation

63
Q

What organism is metronidazole most bactericidal against?

A

obligate anaerobes

64
Q

What is Rifampin bactericidal against?

A

Mycobacteria

Gram + pathogens

65
Q

What adverse effects are seen with Enrofloxacin specifically?

A

Seizures in dogs who are on phenobarbital

66
Q

What groups of bacteria do sulfa drugs kill?

A

Gram positive and negative

67
Q

What is folic acid important for?

A

Purine + DNA synthesis

68
Q

What are the three groups of drugs that interfere with nucleic acid synthesis?

A

Sulfonamides

Fluoroquinolones

Others…

69
Q

Therapeutic use - Difloxacin

A

Dermal + Respiratory + Urinary infections in dogs

Pasteurella

70
Q

Therapeutic Use - Sulfacetamide

A

Only one prepared as a salt at neutral pH

Opthalmic preparations

71
Q

What is the protocol for Nitrofurantoin use in food-producing animals?

A

NOT ALLOWED

72
Q

What is important so that sulfonamides have antibacterial action?

A

Free para-amino group is essenstial

73
Q

What does enrofloxacin work for in regards to swine respiratory disease?

A

A. Pleuropneumoniae

P. Multocida

H. Parasuis

B. bronchoseptica

M. Hyopneumoniae

74
Q

What are the upsides to using potentiated sulfonamides?

A

Bactericidal

Broader spectrum

Reduced rate of resistance

75
Q

What is the protocol for fluoroquinolone use in food animals?

A

Extra label use is not allowed

76
Q

How is danofloxacin used?

A

Single dose or twice 48 hours apart

77
Q

What specific organisms are highly sensitive to sulfa drugs? (8)

A

Pneumococci

Escherichia coli

Nocardia

Actinomyces

Chlamydia

Pneumocystis jirovecii

Some protozoa

Pharmacology II (20 decks)

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