LEC 20 - Inhibitors of Nucleic Acid Synthesis Flashcards by Raegan Chambers

When is nitrofurantoin most effective?

Acidic urine

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

Ricketsia

Fungi

Molds

Mycobacterium tuberculosis

Spirochetes

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Therapeutic Use - Sulfadimethoxine

Long acting

More soluble + less toxic

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How are sulfa drugs excreted from the body?

renal excretion of unchanged drugs + metabolites

Via glomerular filtration + active secretion + passive tubular reaborption

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Therapeutic use - Orbifloxacin + Marbofloxacin

Dermal + Respiratory + Urinary infections - dogs and cats

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Why are sulfonamides safe for mammals?

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

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How are fluoroquinolones distributed throughout the body?

Wide distribution

Including CNS, bone, and prostate

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Therapeutic use - Danofloxacin

Bovine respiratory infections

Mannheimia species

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What are the sulfoamides derivitives of?

Beneze sulfanilamide

Produced by substitution of the amino group

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What are the side effects of trimethoprim or ormetoprim?

Decrease in plasma levels of thyroid hormones

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Why is rifampin combined with erythromycin?

Treatment of rhodococcus equi infections in foals

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What are the three sulfonamide mixtures that are used?

Sulfadiazine + trimethoprim

Sulfamethoxazole + trimetoprim

Sulfadimethoxine + ormetoprim

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What are the side effects seen with sulfa drugs?

Renal crystalluria

KCS

Hypoprothrombinemia + Thrombocytopenia

Arthritis

Reduced sperm counts

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Therapeutic use - Orbifloxacin only

Gram (-) infections in horses

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What is the specific mechanism of action for fluoroquinolones?

Inhibit bacterial DNA gyrase + topoisomerase enzymes that control DNA supercoiling

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How do sulfa drugs cause renal crystalluria?

Precipitaion of sulfonamides in neutral or acidic urine

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

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How is nitrofurantonin used?

lower urinary tract infections in dogs and cats

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

Metronidaole

Rifampin

Nitrofurantoin

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Therapeutic use - Enrofloxacin

Dermal + respiratory + urinary infections

Dogs - cats - brids

(only respiratory infections in cattle)

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What can metronidazole be combined with? Why?

Clindamycin

Prevent pseudomembranous colitis

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What protozoas does metronidazole act against?

Giardia

Trichomonas

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

M. haemolytica

P. Multocida

H. Somni

M. Bovis

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How is rifampin distributed throughout the body?

Wide distribution to cells and tissues

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How is rifampin excreted?

Primarily in the bile

up to 30% can be excreted in the urine

Parent drug can also be excreted

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How are potentiated sulfa drugs handled in the body?

Widely distributed Transcellular fluid = 80% of plasma concentration Bind to albulmin

How is rifampin adminstered?

TID Foals + Dogs + Cats

What adverse effects are seen with fluoroquinolone use?

Reversible erosion of articular cartilage in dogs and foals Retinal degeneration in cats

What is the protocol for Enrofloxacin use in cattle?

Can be given for up to 5 days in cattle Or Single high dose for respiratory infections

What type of inhibtion does sulfa drugs cause with PABA?

Competitive

What are the adverse effects of rifampin?

Hepatotoxicity with pre-existing liver disease Re-oranged colored urine, sweat, and saliva but not harmful

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

Trimethoprim Ormetoprim

What is the specific mechanism of rifampin?

Inhibits DNA-dependent RNA polymerase Prevents initiation of RNA synthesis

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

increased elimination induces microsomal enzymes

Sulfonamides (5)

Sulfamethazine Sulfadimethoxine Sulfachlorpyridazine Sulfacetamide Sulfasalazine

What happens to the bacteria if folic acid is decreased?

Cannot multiply, grow, and survive

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

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

How can nitrofurantoin be adminstered?

Ointment Powder Water-soluble wound dressing

What do potentiated sulfa drugs allow for?

Sequential blockade of folate synthesis

How is sulfasalazine processed in the gut?

Cleaved into sulfapyridine + 5-ASA via the gut bacteria

How are fluoroquinoles metabolized?

Hepatic metabolism

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

Prostate, making it a good therapy for praostatitis

What is different about sulfa drug metabolism in dogs?

There is no acetylation

What type of bacteria tend to be resistant to fluoroquinolones?

Anaerobes

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

M. Haemolytica P. Multocida

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

Dobermans Suldasalazine

Therapeutic Use - Sulfasalazine

Enteric sulfa drug Colitis + IBD in dogs and cats

How does resistance against fluoroquinolones occur?

DNA gyranse + Topoisomerase mutations

How are fluoroquinolones excreted?

Parent drug (15 to 50%) and metabolites excreted in bile and urine

Why is rifampin combined with antifungal agents?

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

Therapeutic Use - Sulfamethazine

Cattle + Sheep + Swine

What so the metabolites of sulfasalazine do?

Sulfapyridine = antibacterial agent 5-ASA = anti-inflammatory

How is the Rifampin metabolized?

Liver Metabolite is antibacterial as well

What is the structure of sulfasalazine?

Linked to a molecule of 5-ASA

What is PABA important for?

Intergral part of folic acid synthesis

What is the use of metronidazole?

Dogs, horse, + cats = severe infections caused by anaerobic pathogens most importantly - brain abcesses + pelvic/genitourinary tract/respiratory infections

When are sulfoamides bactericidial?

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

Therapeutic Use - Sulfachlorpyridazine

Rapidly absorbed + excreted Orally in Cattle under 1m Swine - respiratory + enteric infections (colibacillosis)

Fluoroquinolines (5)

Enrofloxacin Danofloxacin Diflozacin Orbifloxacin Marbofloxacin

How is nitrofurantoin processed in the body?

Reduced by bacteria to reactive intermediates that inhibit nucleic acid synthesis

What is the specific mechanism of action for metronidazole?

Anaerobic bacteria + protozoa takes up drug Reduces to cytotoxic metabolite = DNA disruption

How are potentiated sulfa drugs adminstered?

Orally Injectables

How are potentiated sulfa drugs metabolized in the body?

Via actylation + glucuronide conjugation

What organism is metronidazole most bactericidal against?

obligate anaerobes

What is Rifampin bactericidal against?

Mycobacteria Gram + pathogens

What adverse effects are seen with Enrofloxacin specifically?

Seizures in dogs who are on phenobarbital

What groups of bacteria do sulfa drugs kill?

Gram positive and negative

What is folic acid important for?

Purine + DNA synthesis

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

Sulfonamides Fluoroquinolones Others...

Therapeutic use - Difloxacin

Dermal + Respiratory + Urinary infections in dogs Pasteurella

Therapeutic Use - Sulfacetamide

Only one prepared as a salt at neutral pH Opthalmic preparations

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

NOT ALLOWED

What is important so that sulfonamides have antibacterial action?

Free para-amino group is essenstial

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

A. Pleuropneumoniae P. Multocida H. Parasuis B. bronchoseptica M. Hyopneumoniae

What are the upsides to using potentiated sulfonamides?

Bactericidal Broader spectrum Reduced rate of resistance

What is the protocol for fluoroquinolone use in food animals?

Extra label use is not allowed

How is danofloxacin used?

Single dose or twice 48 hours apart

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

Pneumococci Escherichia coli Nocardia Actinomyces Chlamydia Pneumocystis jirovecii Some protozoa