EXAM 2 CHAPTER 32 PT 1

What is unique about the mechanism of action of sulfonamides?

They inhibit bacterial folic acid synthesis rather than targeting cell walls or protein synthesis.

Why do bacteria need folic acid?

To produce essential molecules needed for DNA synthesis and cell division.

What is the primary mechanism of action of sulfonamides?

Act as false substrates for PABA and inhibit dihydropteroate synthase, preventing folic acid synthesis.

What does PABA stand for?

Para-aminobenzoic acid.

What is the role of PABA in bacteria?

Precursor needed to synthesize folic acid.

Why are sulfonamides considered PABA analogs?

Their chemical structure resembles PABA, allowing them to compete for the same enzyme.

Which enzyme is inhibited by sulfonamides?

Dihydropteroate synthase.

Which enzyme is inhibited by trimethoprim?

Dihydrofolate reductase.

What is the mechanism of action of trimethoprim?

Inhibits dihydrofolate reductase, preventing formation of tetrahydrofolic acid.

What is tetrahydrofolic acid (THFA)?

Active form of folic acid required for bacterial metabolic reactions and DNA synthesis.

What is a potentiated sulfonamide?

A sulfonamide combined with trimethoprim or ormetoprim.

Why are sulfonamides combined with trimethoprim?

They inhibit two sequential steps of folic acid synthesis, producing synergistic activity.

What does synergistic activity mean?

Two drugs produce a greater combined effect than either drug alone.

What is the difference between sulfonamides and potentiated sulfonamides?

Sulfonamides inhibit one folate synthesis step while potentiated sulfas inhibit two sequential steps.

Are standalone sulfonamides bacteriostatic or bactericidal?

Bacteriostatic.

Are potentiated sulfonamides bacteriostatic or bactericidal?

Often bactericidal in susceptible organisms, although resistance may limit effectiveness.

What does bacteriostatic mean?

Inhibits bacterial growth and multiplication without directly killing bacteria.

What does bactericidal mean?

Kills bacteria.

How does the professor recommend classifying sulfonamides for the exam?

Think of sulfonamides primarily as bacteriostatic.

Why are sulfonamides relatively safe for mammalian cells?

Mammals obtain folate from their diet instead of synthesizing it from PABA.

What is the general antimicrobial spectrum of sulfonamides?

Broad spectrum against susceptible gram-positive, gram-negative, and certain protozoal organisms.

Why are sulfonamides considered broad-spectrum drugs in the notes?

They have activity against bacteria and certain protozoa.

What is an important limitation of sulfonamide antimicrobial activity?

Widespread bacterial resistance.

Which bacterial groups are consistently resistant to sulfonamides according to the notes?

Pseudomonas, Chlamydia spp., and Bacteroides.

What is an important resistance concern with Enterobacteriaceae?

Resistance is common, so susceptibility should be confirmed.

What happens when bacteria become resistant to one sulfonamide?

They are generally resistant to other sulfonamides.

Why has sulfonamide resistance become widespread?

Extensive historical use, misuse, and overuse.

What should be done if an organism is resistant to sulfonamides?

Select an effective antibiotic from another class.

What are common clinical uses of sulfonamides?

Uncomplicated UTIs, early respiratory infections, and susceptible skin or soft tissue infections.

Why are sulfonamides useful for uncomplicated UTIs?

They achieve high urinary concentrations.

Are sulfonamides preferred for severe or recurrent infections?

No, resistance and limited effectiveness make them less reliable.

What protozoal infections may respond to sulfonamides?

Certain coccidial infections and other susceptible protozoal diseases.

What organism causes equine protozoal myeloencephalitis (EPM)?

Sarcocystis neurona.

Are sulfonamides currently preferred for EPM treatment?

No, they are older treatment options.

What are the four major sulfonamides discussed in the notes?

Sulfadiazine, sulfadimethoxine, sulfamethazine, and sulfamethoxazole.

What is the brand name of sulfadimethoxine?

Albon.

What is the primary veterinary use of sulfadimethoxine?

Treatment of susceptible bacterial and coccidial infections.

What is important about sulfadimethoxine in lactating dairy cattle?

It is the sulfonamide specifically noted as approved for this use in the US.

What type of sulfonamide is sulfadimethoxine?

Long-acting sulfonamide.

What is a common clinical use of sulfadiazine in horses?

Treatment of susceptible infections when combined with trimethoprim.

What are two brand names for trimethoprim-sulfadiazine?

Tribrissen and Equisul.

What is the most common sulfonamide combination used in horses?

Trimethoprim-sulfadiazine.

What is the typical trimethoprim-to-sulfadiazine ratio?

1:5.

Why is trimethoprim-sulfadiazine commonly dosed twice daily in horses?

Rapid elimination of trimethoprim requires repeated dosing to maintain effective concentrations.

What are common clinical uses of trimethoprim-sulfadiazine in horses?

Early respiratory, urinary, urogenital, skin, soft tissue, and susceptible bone or joint infections.

What is the primary use of sulfamethazine in food animals?

Treatment of susceptible infections, including certain bacterial enteric diseases.

What are common sulfamethazine formulations?

Oral tablets, drinking-water preparations, and sustained-release boluses.

What is a disadvantage of sulfamethazine?

Gastrointestinal irritation, especially diarrhea.

What is the most common human sulfonamide combination discussed?

Trimethoprim-sulfamethoxazole.

What is the brand name of trimethoprim-sulfamethoxazole?

Bactrim DS.

What is the veterinary abbreviation for trimethoprim-sulfamethoxazole?

SMZ/TMP.

What is the common SMZ/TMP tablet strength discussed?

800 mg sulfamethoxazole and 160 mg trimethoprim.

What is the trimethoprim-to-sulfamethoxazole ratio in Bactrim DS?

1:5.

What is a common veterinary use of SMZ/TMP?

Susceptible urinary, respiratory, and soft tissue infections.

What is an off-label use of SMZ/TMP discussed in young cattle?

Treatment of susceptible E. coli bacterial enteritis in preruminating calves.

What is a preruminating calf?

Young calf whose forestomach is not yet functioning as a mature ruminant.

Why are young calves particularly vulnerable to bacterial enteritis?

Severe diarrhea can cause dehydration and electrolyte disturbances.

Are potentiated sulfonamides FDA-approved for food animals in the US according to the notes?

No approved potentiated sulfonamide formulations are listed for food animals.

What is an important concern when using sulfonamides in food animals?

Drug residues and prolonged withdrawal times.

What resource is recommended for checking food animal drug withdrawal intervals?

FARAD.

How are sulfonamides generally absorbed orally in dogs?

Well absorbed, with minimal effect from feeding.

How can feeding affect trimethoprim-sulfonamide absorption in horses?

Feeding may slow absorption without greatly reducing overall absorption.

How are sulfonamides distributed throughout the body?

Widely distributed into body fluids, with variable plasma protein binding.

How much can sulfonamide plasma protein binding vary?

Approximately 50-90%, depending on the drug and species.

Why does sulfonamide pharmacokinetics vary among species?

Differences in metabolism, protein binding, ionization, and elimination.

What is ion trapping?

Accumulation of an ionized drug in a tissue compartment because it cannot easily cross membranes.

Why can trimethoprim accumulate in tissues?

Its weak-base properties favor tissue distribution and ion trapping.

Why can potentiated sulfonamides treat certain CNS infections?

Trimethoprim-sulfonamide combinations can penetrate the CNS.

What is the primary route of sulfonamide elimination?

Renal excretion.

Why do sulfonamides reach high concentrations in urine?

Renal filtration and excretion concentrate the drug in urine.

Why should sulfonamide dosing be adjusted in renal dysfunction?

Impaired elimination can increase drug accumulation and toxicity.

How does acidic urine affect sulfonamide solubility?

Decreases solubility and increases the risk of crystallization.

What effect does alkaline urine have on sulfonamide elimination?

Increases urinary excretion by reducing tubular reabsorption.

What is crystalluria?

Formation of drug crystals in urine.

Why can sulfonamides cause crystalluria?

Poor solubility in acidic urine allows crystals to precipitate in renal tubules.

What factors increase sulfonamide crystalluria risk?

Dehydration, acidic urine, and high drug doses.

What are potential consequences of sulfonamide crystalluria?

Hematuria, renal tubular obstruction, and kidney injury.

How can sulfonamide crystalluria be prevented?

Maintain adequate hydration and monitor renal function.

Which sulfonamide is especially associated with crystalluria in the notes?

Sulfadiazine.

What does KCS stand for?

Keratoconjunctivitis sicca.

What is keratoconjunctivitis sicca?

Dry eye caused by inadequate tear production.

Which species is particularly susceptible to sulfonamide-associated KCS?

Dogs.

Can sulfonamide-associated KCS develop after short treatment courses?

Yes, sometimes within 5-7 days.

Is sulfonamide-associated KCS always reversible?

No, tear production may or may not recover after discontinuation.

What drug is mentioned for managing chronic KCS?

Cyclosporine.

What is a major hypersensitivity concern with sulfonamides?

Delayed hypersensitivity reactions.

What are possible manifestations of sulfonamide hypersensitivity?

Skin eruptions, fever, thrombocytopenia, neutropenia, and anemia.

What is thrombocytopenia?

Decreased platelet count.

What is neutropenia?

Decreased neutrophil count.

What is sulfonamide-associated hepatotoxicity?

Liver injury from hypersensitivity or accumulation of toxic metabolites.

What hematologic complication can occur with prolonged sulfonamide use?

Folate deficiency anemia.

Why can sulfonamides contribute to folate deficiency anemia?

Prolonged interference with folate metabolism can impair blood cell production.

What thyroid disorder is associated with sulfonamides in dogs?

Reversible hypothyroidism.

How can sulfonamides interfere with thyroid function?

Inhibition of thyroid peroxidase reduces thyroid hormone synthesis.

Which sulfonamides are particularly associated with thyroid effects in the notes?

Sulfamethoxazole and sulfadiazine.

What thyroid hormones may change during sulfonamide treatment?

T3, T4, and TSH.

Is sulfonamide-induced hypothyroidism generally reversible?

Yes, thyroid function often normalizes after discontinuation.

What gastrointestinal adverse effects can sulfonamides cause?

Diarrhea, nausea, and vomiting.

Why can antibiotics cause diarrhea?

Disruption of normal gastrointestinal microbial flora.

What is sulfasalazine?

An anti-inflammatory drug used for inflammatory bowel disease, not primarily as an antibiotic.