Pharmacology: Sulfonamides and PABA

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Questions and Answers

Match the following sulfonamides with their respective characteristics:

Sulfacetamide = Short-acting Sulfadimethoxine = Long-acting Sulfamethoxazole = Intermediate-acting Sulfafurazole = Short-acting

Match the following drug combinations with their indicated conditions:

Sulfadoxine + Pyrimethamine = Malaria (2nd line) Sulfamethoxazole + Trimethoprim = General antibacterial use Sulfadiazine + Pyrimethamine = Toxoplasmosis (1st line) Cotrimoxazole = Urinary tract infections

Match the mechanism of action with the corresponding drug:

Trimethoprim = Inhibits dihydrofolate reductase Sulfamethoxazole = Competes with PABA Sulfadiazine = Inhibits bacterial dihydrofolic acid synthesis Cotrimoxazole = Broad-spectrum antibacterial activity

Match the following terms with their definitions:

Bacteriostatic = Inhibits bacterial growth Dihydropteroate synthetase = Targeted by sulfonamides Folic acid synthesis = Human dietary intake Tetrahydrofolic acid = Essential for purine and amino acid synthesis Signup and view all the answers

Match the following bacterial infections with the sulfonamides used:

Nocardia infections = Sulfonamides Urinary tract infections = Trimethoprim Shigellosis = Trimethoprim Invasive salmonella infections = Cotrimoxazole Signup and view all the answers

Match the sulfonamide with its typical use:

Sulfamethoxypyridazine = Long-acting treatment Sulfisomidine = Short-acting treatment Sulfametopyrazine = Treatment of bacterial infections Sulfadoxine = Malaria combination therapy Signup and view all the answers

Match the following sulfonamide types with their longevity:

Short-acting = Sulfafurazole Intermediate-acting = Sulfamethoxazole Long-acting = Sulfadimethoxine Signup and view all the answers

Match the following drugs with their primary adverse effects:

Trimethoprim = Skin Rash Cotrimoxazole = Megaloblastic anemia Sulfonamides = Crystalluria Methotrexate = Leukopenia Signup and view all the answers

Match the following substances with their characteristic pharmacokinetics:

Sulfasalazine = Reserved for chronic inflammatory bowel disease Trimethoprim = Weak base with high concentration in acidic fluids Cotrimoxazole = Can be administered IV for severe pneumonia Sulfonamides = Widely distributed throughout body fluids Signup and view all the answers

Match the following conditions with their appropriate treatment mechanisms:

UTI = Trimethoprim selectively inhibits bacterium Malaria = Sulfadoxine + Pyrimethamine administration Toxoplasmosis = Sulfadiazine + Pyrimethamine treatment Broad-spectrum infections = Cotrimoxazole application Signup and view all the answers

Match the following drugs with their effect on warfarin and methotrexate serum levels:

Sulfonamides = Increase serum levels Trimethoprim = No effect Cotrimoxazole = Increase serum levels Folic acid = Reverses effects Signup and view all the answers

Match the following drug-related issues with their solutions:

Megaloblastic anemia = Folinic acid administration Skin rash from Cotrimoxazole = Discontinue the drug G6PD deficiency = Avoid certain antibiotics Crystalluria = Hydration and alkali therapy Signup and view all the answers

Match the following drugs with their method of administration:

Cotrimoxazole = Oral and IV forms Sulfasalazine = Oral only Trimethoprim = Oral only Silver sulfadiazine = Topical application Signup and view all the answers

Match the following lab results with their associated drug effects:

Elevated serum warfarin = Sulfamethoxazole interaction Leukopenia = Trimethoprim toxicity Hemolytic anemia = G6PD deficiency Nausea and vomiting = Cotrimoxazole side effect Signup and view all the answers

Match the following pharmacological properties with the corresponding drugs:

Trimethoprim = Rapid oral absorption Sulfonamides = Acetylated and conjugated in the liver Cotrimoxazole = Excreted in urine Sulfasalazine = Not applied topically Signup and view all the answers

Match the following adverse effects with their descriptions:

Sulfamethoxazole = Displacement from serum albumin leading to increased drug levels Trimethoprim = Risk of granulocytopenia Cotrimoxazole = May cause thrombocytopenia Sulfonamides = May precipitate crystalluria in acidic urine Signup and view all the answers

Match the following conditions with their respective treatments:

Bacterial conjunctivitis = Sodium sulfacetamide ophthalmic solution Burn wounds = Silver sulfadiazine MRSA infection = Cotrimoxazole Toxoplasmosis = Trimethoprim-sulfamethoxazole Signup and view all the answers

Match the following types of drug resistance with their descriptions:

Sulfonamide resistance = Bacteria that can obtain folate from the environment Trimethoprim resistance = Altered dihydrofolate reductase Cotrimoxazole resistance = Less frequently encountered Efflux pump resistance = Decreased drug permeability Signup and view all the answers

Match the following adverse effects with their corresponding explanations:

Crystalluria = Nephrotoxicity due to drug concentration Hypersensitivity = Stevens-Johnson syndrome Kernicterus = Bilirubin displacement in newborns Hematopoietic disturbances = Blood dyscrasias and anaemia Signup and view all the answers

Match the following infections with their specific treatments:

Pneumocystis jirovecii pneumonia (PCP) = Trimethoprim-sulfamethoxazole Nocardiosis = Cotrimoxazole Stenotrophomonas maltophilia = Cotrimoxazole Chloramphenicol-resistant salmonella = Trimethoprim-sulfamethoxazole Signup and view all the answers

Match the following topical agents with their functions:

Mafenide acetate = Used for burn treatment Silver sulfadiazine = Drug of choice for burn wounds Sodium sulfacetamide = Adjunctive therapy for trachoma Bacterial conjunctivitis = Treatment with ophthalmic solution Signup and view all the answers

Match the following bacteria with their associated resistance types:

E. coli = Cotrimoxazole resistance MRSA = Cotrimoxazole resistance Acinetobacter = Efflux pump resistance Pseudomonas aeruginosa = Altered drug permeability Signup and view all the answers

Match the following features of sulfonamide usage with their implications:

Adequate hydration = Prevention of crystalluria Hypersensitivity reactions = Risk of angioedema Kernicterus in newborns = Bilirubin enters CNS Cotrimoxazole use = Effective against MRSA Signup and view all the answers

Match the following adverse effects with the related clinical context:

Rashes = Hypersensitivity associated with sulfonamides Granulocytopenia = Hematopoietic disturbances Acid-base imbalance = Mafenide acetate absorption from burns Thrombocytopenia = Blood dyscrasias with sulfonamides Signup and view all the answers

Study Notes

Sulfonamides and p-aminobenzoic acid (PABA)

Sulfonamides are structural analogs of PABA.
They are used for bacterial infections.
They are divided into three categories: short-acting, intermediate-acting, and long-acting.

Mechanism of action

Humans obtain folic acid from their diet to synthesize tetrahydrofolic acid.
Bacteria synthesize folate derivatives because their cell walls are impermeable to folic acid and other folates.
Sulfonamides compete with PABA for the bacterial enzyme dihydropteroate synthetase, inhibiting bacterial dihydrofolic acid synthesis.
This inhibits the synthesis of essential cofactors that humans do not have.
Trimethoprim inhibits dihydrofolate reductase, inhibiting the synthesis of tetrahydrofolic acid necessary for purine, pyrimidine, and amino acid synthesis.
Trimethoprim has stronger affinity for bacterial dihydrofolate reductase than for human dihydrofolate reductase.
Both sulfonamides and trimethoprim are bacteriostatic.

Antibacterial spectrum

Sulfonamides are seldom prescribed alone.
They are effective against nocardia infections and enterobacteriaceae in the urinary tract.
Trimethoprim can be used alone to treat urinary and respiratory tract infections, prostatitis, shigellosis, and invasive salmonella infections.
It is 20 to 50 times more potent than sulfonamides.
Cotrimoxazole has a broader spectrum than sulfonamides alone.
It is used to treat UTIs, respiratory tract infections, Pneumocystis jirovecii pneumonia (PCP), toxoplasmosis, and ampicillin- or chloramphenicol-resistant salmonella infections.
It is effective against community-acquired skin and soft tissue infections caused by MRSA.
It is the drug of choice for infections caused by susceptible Nocardia species and Stenotrophomonas maltophilia.

Resistance

Sulfonamide resistance can occur through plasmid transfer or random mutations.
Resistance mechanisms include:
- Bacteria obtaining folate from the environment.
- Altered dihydropteroate synthetase (altered target).
- Decreased drug permeability.
- Increased PABA production.
Trimethoprim resistance mechanisms include:
- Altered dihydrofolate reductase (low affinity towards the drug).
- Efflux pumps.
- Decreased drug permeability.
Cotrimoxazole resistance is less common but has been reported in E. coli and MRSA.

Topical agents

Sodium sulfacetamide ophthalmic solution or ointment is effective in treating bacterial conjunctivitis and as adjunctive therapy for trachoma.
Mafenide acetate is used topically but can cause pain.
It can be absorbed from burn sites, increasing the risk of acid-base imbalance.
Silver sulfadiazine is the drug of choice for burn wounds and is less toxic.

Adverse effects

Sulfonamides:
- Crystalluria (nephrotoxicity): Adequate hydration and alkalinization of urine can prevent this problem.
- Hypersensitivity: Rashes, angioedema, Stevens-Johnson syndrome.
- Hematopoietic disturbances: Hemolytic anemia in G6PD deficient patients, granulocytopenia, thrombocytopenia, agranulocytosis, aplastic anemia, and other blood dyscrasias.
- Kernicterus: Occurs in newborns. Sulfa drugs displace bilirubin from serum albumin, allowing it to enter the CNS. The blood-brain barrier is not fully developed in newborns.
- Drug potentiation: Increases serum levels of warfarin and methotrexate by displacing them from serum albumin.
Trimethoprim:
- Folic acid deficiency: Megaloblastic anemia, leukopenia, and granulocytopenia, especially in pregnant or poorly nourished patients.
- This can be reversed by administering folinic acid (10 mg), which does not enter bacteria.
Cotrimoxazole (trimethoprim + sulfamethoxazole):
- Skin rash (common).
- Nausea and vomiting (most common).
- Megaloblastic anemia, leukopenia, and thrombocytopenia can occur and have been fatal.
  - This can be reversed by administration of folinic acid.
- Hemolytic anemia in patients with G6PD deficiency.
- Drug potentiation: Increases serum levels of warfarin and methotrexate.

Pharmacokinetics

Sulfonamides:
- Well absorbed orally, except for sulfasalazine.
- Oral sulfasalazine is reserved for chronic inflammatory bowel disease (e.g., ulcerative colitis) as its metabolites (sulfapyridine and 5-aminosalicylate) exert anti-inflammatory effects.
- Not applied topically due to sensitization. However, creams of silver sulfadiazine/mafenide acetate can reduce burn-associated sepsis by preventing bacterial colonization.
- IV form is used for patients unable to swallow.
- Protein bound and widely distributed throughout the body fluids, including CSF even in the absence of inflammation.
- Acetylated and conjugated in the liver; metabolites have no antimicrobial activity but are toxic at neutral/acidic pH (causing crystalluria).
- Eliminated by glomerular filtration and secretion.
Trimethoprim:
- Rapid oral absorption.
- Wide distribution, including the CSF.
- Weak base that concentrates in acidic prostatic and vaginal fluids.
- 60-80% is excreted unchanged via the kidneys.
Cotrimoxazole:
- Oral (preferred) and IV (for severe pneumonia caused by PCP) routes.
- Wide distribution, including the CSF.
- Both parent drugs and their metabolites are excreted in the urine.

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Description

This quiz delves into the role of sulfonamides as structural analogs of PABA and their application in treating bacterial infections. It covers their mechanism of action, including their competition with PABA in the synthesis of folate derivatives necessary for bacteria. Assess your understanding of these essential pharmacological concepts.