Notes on Sulfonamides Pharmacokinetics, Side Effects, Drug Interaction and MCQ for GPAT, NEET PG, NIPER JEE and Competitive exams

Notes on Sulfonamides Pharmacokinetics, Side Effects, Drug Interaction and MCQ for GPAT, NEET PG, NIPER JEE and Competitive exams

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Pharmacokinetics

  • Absorption:
    • Well-absorbed orally from the gastrointestinal tract.
    • Peak plasma levels: 2-6 hours post-dose.
    • Food may delay absorption but doesn’t reduce total amount absorbed.
  • Distribution:
    • Widely distributed in body fluids (e.g., pleural, peritoneal, ocular fluids).
    • Crosses placenta and blood-brain barrier (BBB).
    • Protein binding: 20-90% (varies by specific sulfonamide).
  • Metabolism:
    • Hepatic metabolism via acetylation (in the liver).
    • Produces inactive metabolites (e.g., N-acetyl derivatives).
    • Trick: “Sulfonamides get ‘Acetylated’ in the liver – think ‘A’ for Acetylation and Absorption.”
  • Excretion:
    • Primarily renal (glomerular filtration + tubular secretion).
    • Both unchanged drug and metabolites excreted in urine.
    • Half-life: 6-12 hours (short-acting) or longer for sulfadiazine (up to 17 hours).
    • Trick: “Sulfonamides Exit via Kidneys – think ‘S-E-K’ (Sulfonamide-Excretion-Kidney).”

Side Effects (with Tricks)

  • Common Side Effects:
    1. Hypersensitivity: Rash, fever, Stevens-Johnson syndrome (SJS).
      • Trick: “Sulfa makes Skin Sizzle” (S for Sulfa, S for Skin issues).
    2. Crystalluria: Precipitation in urine → kidney stones.
      • Trick: “Sulfa Crystals Clog Kidneys” (C for Crystals, C for Clog).
    3. Hematologic: Hemolytic anemia (especially in G6PD deficiency), thrombocytopenia.
      • Trick: “Sulfa Slashes Blood” (S for Sulfa, S for Slash hemoglobin).
    4. GI Upset: Nausea, vomiting, diarrhea.
      • Trick: “Sulfa Sickens Stomach” (S for Sulfa, S for Stomach).
  • Rare but Serious: 5. Kernicterus: In newborns due to displacement of bilirubin from albumin.
    • Trick: “Sulfa Kicks Bilirubin” (K for Kernicterus, K for Kick).
    1. Hepatitis: Liver toxicity.
      • Trick: “Sulfa Harms Hepatic House” (H for Hepatitis, H for Hepatic).

Therapeutic Uses

  • Antibacterial Action:
    • Mechanism: Inhibit folate synthesis (competitive inhibition of dihydropteroate synthase).
    • Bacteriostatic against Gram-positive and Gram-negative bacteria.
  • Key Uses:
    1. Urinary Tract Infections (UTIs): e.g., Sulfamethoxazole (with trimethoprim in Bactrim).
      • Trick: “Sulfa Unblocks Urinary” (U for UTI, U for Unblock).
    2. Respiratory Infections: e.g., Pneumonia (Pneumocystis jirovecii in immunocompromised).
      • Trick: “Sulfa Rescues Respiration” (R for Respiratory, R for Rescue).
    3. Nocardiosis: Caused by Nocardia spp.
      • Trick: “Sulfa Nixes Nocardia” (N for Nocardia, N for Nix).
    4. Toxoplasmosis: Sulfadiazine + pyrimethamine.
      • Trick: “Sulfa Tames Toxo” (T for Toxo, T for Tame).
    5. Burns/Skin Infections: Topical (e.g., silver sulfadiazine).
      • Trick: “Sulfa Soothes Skin” (S for Skin, S for Soothe).

Drug Interactions

  • Key Interactions:
    1. Warfarin: ↑ Anticoagulant effect (displaces from protein binding).
      • Trick: “Sulfa Worsens Warfarin’s Work” (W for Warfarin, W for Worsen).
    2. Methotrexate: ↑ Toxicity (displaces from protein binding).
      • Trick: “Sulfa Magnifies Methotrexate Mess” (M for Methotrexate, M for Magnify).
    3. Phenytoin: ↑ Levels (inhibits metabolism).
      • Trick: “Sulfa Pumps Phenytoin” (P for Phenytoin, P for Pump).
    4. Sulfonylureas (e.g., glipizide): ↑ Hypoglycemia risk.
      • Trick: “Sulfa Sweetens Sugar-lowering” (S for Sulfonylurea, S for Sweeten).
    5. Diuretics: ↑ Risk of thrombocytopenia (e.g., with thiazides).
      • Trick: “Sulfa + Diuretics Drain Blood” (D for Diuretics, D for Drain).

Chart: Sulfonamides Overview

Aspect Details Trick/Notes
Absorption Oral, 2-6 hr peak “Sulfa Absorbs After Apples” (food delays)
Distribution Wide, crosses BBB/placenta “Sulfa Spreads Swiftly”
Metabolism Hepatic acetylation “A for Acetylation”
Excretion Renal (urine) “S-E-K: Sulfa Exits Kidney”
Side Effects Crystalluria, rash, hemolytic anemia “Sulfa Crystals Clog, Skin Sizzles”
Therapeutic Uses UTIs, pneumonia, burns “Sulfa Unblocks Urinary, Rescues Respiration”
Drug Interactions Warfarin, methotrexate, phenytoin “Sulfa Worsens Warfarin, Magnifies Methotrexate”

Chart: Pharmacokinetic Parameters of Sulfonamides

Parameter Details Notes
Absorption Well-absorbed orally; peak plasma levels in 2-6 hours Food delays absorption but doesn’t reduce total amount absorbed
Bioavailability High (70-100% for most sulfonamides) Varies slightly depending on formulation and specific drug
Distribution Widely distributed; crosses BBB and placenta; Vd: 0.15-0.4 L/kg Protein binding: 20-90% (e.g., sulfamethoxazole ~70%, sulfadiazine ~50%)
Metabolism Hepatic via acetylation (N-acetyl derivatives); some Phase II conjugation Inactive metabolites formed; slow acetylators at risk of toxicity
Half-Life (t½) Short-acting: 6-12 hours (e.g., sulfamethoxazole); Long-acting: up to 17 hours (e.g., sulfadiazine) Half-life prolonged in renal impairment
Excretion Primarily renal (glomerular filtration + tubular secretion); 10-50% unchanged Urine pH affects solubility (alkaline urine reduces crystalluria risk)
Time to Peak (Tmax) 2-6 hours post-oral dose Delayed by food intake
Clearance Renal clearance: 20-60 mL/min; total clearance depends on protein binding Reduced in renal failure; dose adjustment needed

Chart: Pharmacokinetics of Individual Sulfonamides

Sulfonamide Absorption Bioavailability Distribution (Vd) Protein Binding Metabolism Half-Life (t½) Excretion Time to Peak (Tmax)
Sulfamethoxazole Well-absorbed orally; delayed by food ~70-90% 0.2-0.4 L/kg ~70% Hepatic (acetylation) 9-12 hours Renal (30% unchanged) 2-4 hours
Sulfadiazine Well-absorbed orally ~80-100% 0.15-0.3 L/kg ~50-60% Hepatic (acetylation) 10-17 hours Renal (40-60% unchanged) 3-6 hours
Sulfisoxazole Rapidly absorbed orally ~90-100% 0.2-0.35 L/kg ~85-90% Hepatic (acetylation) 4-7 hours Renal (50% unchanged) 1-4 hours
Sulfasalazine Poorly absorbed (10-30%); mostly in colon ~10-15% (systemic) 0.1-0.2 L/kg (systemic) ~99% Colonic bacteria → sulfapyridine 5-10 hours (sulfapyridine) Renal (sulfapyridine); fecal (unabsorbed) 3-6 hours (sulfapyridine)

Notes on Each Sulfonamide

  1. Sulfamethoxazole:
    • Commonly paired with trimethoprim (e.g., Bactrim).
    • Moderate half-life; suitable for twice-daily dosing.
    • Wide distribution, including CSF penetration.
  2. Sulfadiazine:
    • Longer half-life; used in toxoplasmosis (with pyrimethamine).
    • Good CNS penetration, making it ideal for brain infections.
    • Slightly lower protein binding than others.
  3. Sulfisoxazole:
    • Shorter half-life; rapid onset and clearance.
    • High protein binding reduces free drug availability.
    • Often used for UTIs due to rapid renal excretion.
  4. Sulfasalazine:
    • Unique: Poor systemic absorption; acts locally in the gut.
    • Metabolized by colonic bacteria into sulfapyridine (active systemic metabolite) and 5-ASA (local anti-inflammatory).
    • Used for inflammatory bowel disease (e.g., ulcerative colitis).

Multiple-Choice Questions (MCQs) on Pharmacokinetic Parameters of Sulfonamides

  1. What is the primary route of excretion for sulfonamides?
    • A) Hepatic metabolism
    • B) Renal excretion
    • C) Biliary excretion
    • D) Pulmonary elimination
    • Answer: B) Renal excretion
    • Explanation: Sulfonamides are excreted primarily via the kidneys through glomerular filtration and tubular secretion.
  2. How long does it typically take for sulfonamides to reach peak plasma concentration after oral administration?
    • A) 30 minutes to 1 hour
    • B) 2-6 hours
    • C) 8-12 hours
    • D) 24 hours
    • Answer: B) 2-6 hours
    • Explanation: Sulfonamides achieve peak levels in 2-6 hours, though food can delay this.
  3. Which of the following best describes the protein binding of sulfonamides?
    • A) Negligible (<10%)
    • B) Moderate to high (20-90%)
    • C) Complete (100%)
    • D) Only in acidic environments
    • Answer: B) Moderate to high (20-90%)
    • Explanation: Protein binding varies (e.g., sulfamethoxazole ~70%), affecting distribution and interactions.
  4. What is the typical half-life of short-acting sulfonamides like sulfamethoxazole?
    • A) 1-2 hours
    • B) 6-12 hours
    • C) 24-36 hours
    • D) 48 hours
    • Answer: B) 6-12 hours
    • Explanation: Short-acting sulfonamides have a half-life of 6-12 hours, while long-acting ones (e.g., sulfadiazine) may extend to 17 hours.
  5. Where are sulfonamides primarily metabolized?
    • A) Kidneys
    • B) Liver
    • C) Small intestine
    • D) Lungs
    • Answer: B) Liver
    • Explanation: Hepatic acetylation converts sulfonamides into inactive metabolites.
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