Pharmacology 50s and nucleic acid inhibitors Flashcards

Question

Fluoroquinolones absorption

Answer 1

**Well absorbed orally in monogastrics** * Exception – ciprofloxacin * Poorly absorbed in cats * Really poorly absorbed in horses Exception – enrofloxacin * Oral in kittens – **chelation on milk diet**

Answer 2

Distribute well to the tissues Penetrate well **intracellularly** * Enrofloxacin reaches the highest concentration in the cells * Highest **lipid solubility** and volume of distribution

Answer 3

**Enrofloxacin is metabolized in vivo to ciprofloxacin** * Active metabolite * Metabolism is species and age dependent * 41% cattle, 36% dogs, 17% horses * 0% foal, 16% kittens Elimination mainly via the **kidney** * EXCEPTION - Pradofloxacin - hepatic elimination * Highly effective for **treating resistant UTIs** * Activity is pH dependent (reduced in acidic environments) Half-life is moderate * **Once daily dosing due to PAE** * Exception: **twice daily ciprofloxacin in dogs**

Answer 4

**Cartilage toxicity – severe!** * Chelation of Mg++ in cartilage decreases adherence of chondrocytes * Lesions exacerbated by **weight-bearing = more severe** * **Dogs and FOALS** most susceptible, cats and calves resistant **Ocular toxicity** * **Cats** * Enrofloxacin #1 * Dose dependent * **Retinal degeneration, blindness**

Answer 5

May **inhibit the clearance of some drugs** (ie theophylline) **Chelation** * Antacids, sucralfate, and multiple vitamins (iron) * Should not be administered orally at the same time as a FQ (prevent absorption)

Answer 6

**Alteration of target enzyme (DNA gyrase)** * Not plasmid mediated Reduced access through altered porins * **Pseudomonas** * Resistance **may develop during treatment** (esp enro) * Not recommended as a systemic treatment (topical OK)

Answer 7

sulfa drugs **Extralabel use prohibited in adult dairy cattle!!!** **bacteriostatic**

Answer 8

Sulfonamide (bacteriostatic) plus dihydrofolate reductase inhibitor (bacteriostatic)= **bacteriocidal** **synnergism** **Ruminants don’t absorb DHFRIs** (use just sulfas alone)

Answer 9

**inhibit folic acid synthesis** at 2 different stages (bacteria must produce their own folic acid) **Broad Spectrum** * First line choice for **pyodermas, UTIs and soft tissue** infections (If caused by susceptible bacteria) * Resistance to these combinations is increasing * May be effective in some cases of **MRSA/MRSP** Effective against **protozoa** **NOT against Anaerobes**

Answer 10

Well **absorbed orally** Good tissue distribution (**extracellular and intracellular**) * Sulfadiazine and pyrimethamine best * Includes CNS, prostate Extensive **metabolism in the liver** * Moderate half-life, allowing for once or twice daily dosing Mainly **renal elimination** Time-dependent

Answer 11

**Minimal in horses** (Occasional diarrhea) **Minimal in cats** (Taste and difficulty pilling, **SLOBBERS!!**!) Safe in ruminants Safe in swine **Numerous in dogs** * Altered metabolism * Breed susceptibility * Incidence 0.25%

Answer 12

**Lack of N-acetyltransferase** * Detoxifying enzyme * Without it, **toxic metabolites** produced * Dobermans, Rottweilers **Allergic/immune** * polyarthritis, lymphadenopathy, fever, Glomerulonephropathy * **REVERSIBLE** **Cutaneous** * ulcerations * **REVERSIBLE** **Hepatopathy and Thrombocytopenia** * lower recovery rate **Keratoconjunctivitis sicca** * aka dry eye * not reversible **Hypothyroidism** * Block formation of thyroxine and thyronine * **Reversible** Bone marrow supression (rare) Urine crystal formation

Answer 13

**Lack of N-acetyltransferase** * Detoxifying enzyme * Without it, **toxic metabolites** produced * Dobermans, Rottweilers **Allergic/immune** * polyarthritis, lymphadenopathy, fever, Glomerulonephropathy * **REVERSIBLE** **Cutaneous** * ulcerations * **REVERSIBLE** **Hepatopathy and Thrombocytopenia** * lower recovery rate **Keratoconjunctivitis sicca** * aka dry eye * not reversible **Hypothyroidism** * Block formation of thyroxine and thyronine * **Reversible** Bone marrow supression (rare) Urine crystal formation

Answer 14

Sulfonamides * Increased synthesis of **PABA ( competes for target)** * **PABA produced in abscesses** * Procaine in PPG metabolized to PABA (TMS-PPG DDI?) * Low affinity or resistant DHP synthetase (plasmid) DHFRIs * **Increased production of normal DHFR** * **Low affinity** or resistant DHFR synthetase (plasmid)

Answer 15

**Metronidazole**, ronidazole, tinidazole Use **prohibited in food animals!!!**

Answer 16

* **Absorbed** into bacterial cell (lipophilic) * **Reduction** of antibiotic by nitroreductases * **Formation of highly reactive metabolites** * **Disruption of bacterial DNA** * Bacterial cell death **(bactericidal)** **Only active in anaerobic conditions** * Oxygen competes with antibiotic for electrons necessary for nitroreductase rxn

Answer 17

**Only active in anaerobic conditions** * Oxygen competes with antibiotic for electrons necessary for nitroreductase rxn * **ANAEROBES!**

Answer 18

Well **absorbed orally** **Well distributed** into tissues * Including CNS and abscesses Rapid onset, **bactericidal** Excellent activity against Bacteroides and Clostridium Less active against Actinomyces and Proprionobacterium Most common use – “Giardia” | Nitroimidazole

Answer 19

**Neurotoxicity** * Severe **ataxia, vertical or rotary nystagmus, seizures** * Signs are often preceded by anorexia and vomiting * Typically **reversible** * High doses, chronic dosing, rapid IV administration, neonates * Ronidazole in cats May be mutagenic/carcinogenic: **Use prohibited in food animals!!** Anorexia (tastes bad!)

Answer 20

Spectrum: **Gram-positive and Gram-negative bacteria** Mechanism: **inhibits bacterial DNA-dependent RNA polymerase** Mostly **bacteriostatic** (can be bactericidal) Noted for **intracellular** activity (**Abscesses!**) Low incidence of resistance currently Noted for **creating resistance DURING use** Sometimes used as a monotherapy for treatment of **MRSP pyoderma** (Culture dependent) * Nearly always **combined with second drug in horses** * Macrolide plus rifampin for treatment of **R. equi in foals** * Co-administration of rifampin decreases clarithromycin bioavailability 90%! * Still effective (synergism) and still used…for now Low order of toxicity **Dogs – hepatic enzymes and hepatotoxicity** an increasing concern Turns urine, sweat, and tears a red or orange color