Running head: From Pharmacological Mechanism to Precision Medicine (BBS3012) 1
From Pharmacological Mechanism to
Precision Medicine (BBS3012)
Case 7, 8
Name
Institution
Course
Tutor
Date
,From Pharmacological Mechanism to Precision Medicine (BBS3012) 2
CASE 7 – WHEN AGE MATTERS
LGs:
Part A (At the pediatrician’s department)
1. Pharmacodynamics and pharmacokinetics of sulphadimidine,
ampicillin and chloramphenicol?
Sulfanilamide is an anti-infective agent and it has a spectrum of antimicrobial action
similar to other sulfonamides. Sulfamethazine is bacteriostatic in nature.
→ Toxicity
Sulfamethazine may cause nausea, vomiting, diarrhea and hypersensitivity reactions.
Hematologic effects such as anemia, agranulocytosis, thrombocytopenia and
hemolytic anemia with glucose-6-pohpshate dehydrogenase deficiency may also
occur. Sulfamethoxazole may displace bilirubin from albumin binding sites
Sulphadimidine causing jaundice or kernicterus in newborns.
Indication For the treatment of bacterial infections causing bronchitis, prostatitis and urinary
tract infections.
Mechanism of action Sulfonamides inhibit the enzymatic conversion of pteridine and paminobenzoic acid
(PABA) to dihydropteroic acid by competing with PABA for biding to
dihydrofolate synthetase, an intermediate of tetrahydrofolic acid (THF) synthesis.
THF is required to the synthesis of purines and dTMP and inhibition of its synthesis
inhibits bacterial growth. (Pyrimethamine and trimethoprim inhibit dihydrofolate
reductase, another step in THF synthesis, and therefore act synergistically with the
sulfonamides).
,From Pharmacological Mechanism to Precision Medicine (BBS3012) 3
Pharmacodynamics Sulfamethazine is a sulfonamide drug that inhibits bacterial synthesis of dihydrofolic
acid by competing with para-aminobenzoic acid (PABA) for binding to
dihydropteroate synthase (dihydrofolate synthetase). This prevents the normal
bacterial utilization of PABA for the synthesis of folic acid (pteroylglutamic
acid).
Inhibition of dihydrofolic acid synthesis decreases the synthesis of bacterial
nucleotides and DNA. Sensitive microorganisms are those that must synthesize
their own folic acid: bacteria that can use preformed folate are not affected.
Absorption Rapidly absorbed following oral administration. Approximately 70 to 100% of the
oral dose is absorbed and sulfonamide can be found in the urine within 30 minutes of
ingestion. The small intestine is the major site of absorption, but some of the drug is
absorbed from the stomach.
Distribution Peak plasma levels are achieved in 2 to 6 hours, depending on the drug.
All sulfonamides are bound in varying degree to plasma proteins, particularly to
albumin.
Sulfonamides are distributed throughout all tissues of the body. The sulfonamides
may enter the pleural, peritoneal, synovial, ocular and similar body fluids and may
reach concentrations therein that are 50% to 80% of the simultaneously determined
concentration in blood.
Metabolism Sulfonamides undergo metabolic alterations in vivo, especially in the liver. The major
metabolic derivative is the N4-acetylated sulfonamide.
Acetylation, which occurs to a different extent with each agent, is disadvantageous
, From Pharmacological Mechanism to Precision Medicine (BBS3012) 4
because the resulting products have no antibacterial activity yet retain the toxic
potential of the parent substance.
Excretion Sulfonamides are eliminated from the body partly as the unchanged drug and partly as
metabolic products. The largest fraction is excreted in the urine, and the half-life of
sulfonamides in the body thus depends on the renal function.
Chloramphenicol An antibiotic with a simple structure; was the first broad-spectrum antibiotic to be
discovered. It acts by interfering with bacterial protein synthesis and is mainly
bacteriostatic. It is effective against wide variety of microorganisms but due to serious
side-effects in humans it is usually reserved for the treatment of serious and life-
threatening infections.
Usual dosage is 50-100 mg/kg/d.
→ Toxicity
Chloramphenicol causes dose-related reversible suppression of red cell production at
dosages exceeding 50 mg/kg/day after 1-2 weeks.
Indication Used in treatment of cholera, as it destroys the vibrios and decreases diarrhea. It is
effective against tetracycline-resistant vibrios. It is also used in eye drops or ointment to
treat bacterial conjunctivitis.
From Pharmacological Mechanism to
Precision Medicine (BBS3012)
Case 7, 8
Name
Institution
Course
Tutor
Date
,From Pharmacological Mechanism to Precision Medicine (BBS3012) 2
CASE 7 – WHEN AGE MATTERS
LGs:
Part A (At the pediatrician’s department)
1. Pharmacodynamics and pharmacokinetics of sulphadimidine,
ampicillin and chloramphenicol?
Sulfanilamide is an anti-infective agent and it has a spectrum of antimicrobial action
similar to other sulfonamides. Sulfamethazine is bacteriostatic in nature.
→ Toxicity
Sulfamethazine may cause nausea, vomiting, diarrhea and hypersensitivity reactions.
Hematologic effects such as anemia, agranulocytosis, thrombocytopenia and
hemolytic anemia with glucose-6-pohpshate dehydrogenase deficiency may also
occur. Sulfamethoxazole may displace bilirubin from albumin binding sites
Sulphadimidine causing jaundice or kernicterus in newborns.
Indication For the treatment of bacterial infections causing bronchitis, prostatitis and urinary
tract infections.
Mechanism of action Sulfonamides inhibit the enzymatic conversion of pteridine and paminobenzoic acid
(PABA) to dihydropteroic acid by competing with PABA for biding to
dihydrofolate synthetase, an intermediate of tetrahydrofolic acid (THF) synthesis.
THF is required to the synthesis of purines and dTMP and inhibition of its synthesis
inhibits bacterial growth. (Pyrimethamine and trimethoprim inhibit dihydrofolate
reductase, another step in THF synthesis, and therefore act synergistically with the
sulfonamides).
,From Pharmacological Mechanism to Precision Medicine (BBS3012) 3
Pharmacodynamics Sulfamethazine is a sulfonamide drug that inhibits bacterial synthesis of dihydrofolic
acid by competing with para-aminobenzoic acid (PABA) for binding to
dihydropteroate synthase (dihydrofolate synthetase). This prevents the normal
bacterial utilization of PABA for the synthesis of folic acid (pteroylglutamic
acid).
Inhibition of dihydrofolic acid synthesis decreases the synthesis of bacterial
nucleotides and DNA. Sensitive microorganisms are those that must synthesize
their own folic acid: bacteria that can use preformed folate are not affected.
Absorption Rapidly absorbed following oral administration. Approximately 70 to 100% of the
oral dose is absorbed and sulfonamide can be found in the urine within 30 minutes of
ingestion. The small intestine is the major site of absorption, but some of the drug is
absorbed from the stomach.
Distribution Peak plasma levels are achieved in 2 to 6 hours, depending on the drug.
All sulfonamides are bound in varying degree to plasma proteins, particularly to
albumin.
Sulfonamides are distributed throughout all tissues of the body. The sulfonamides
may enter the pleural, peritoneal, synovial, ocular and similar body fluids and may
reach concentrations therein that are 50% to 80% of the simultaneously determined
concentration in blood.
Metabolism Sulfonamides undergo metabolic alterations in vivo, especially in the liver. The major
metabolic derivative is the N4-acetylated sulfonamide.
Acetylation, which occurs to a different extent with each agent, is disadvantageous
, From Pharmacological Mechanism to Precision Medicine (BBS3012) 4
because the resulting products have no antibacterial activity yet retain the toxic
potential of the parent substance.
Excretion Sulfonamides are eliminated from the body partly as the unchanged drug and partly as
metabolic products. The largest fraction is excreted in the urine, and the half-life of
sulfonamides in the body thus depends on the renal function.
Chloramphenicol An antibiotic with a simple structure; was the first broad-spectrum antibiotic to be
discovered. It acts by interfering with bacterial protein synthesis and is mainly
bacteriostatic. It is effective against wide variety of microorganisms but due to serious
side-effects in humans it is usually reserved for the treatment of serious and life-
threatening infections.
Usual dosage is 50-100 mg/kg/d.
→ Toxicity
Chloramphenicol causes dose-related reversible suppression of red cell production at
dosages exceeding 50 mg/kg/day after 1-2 weeks.
Indication Used in treatment of cholera, as it destroys the vibrios and decreases diarrhea. It is
effective against tetracycline-resistant vibrios. It is also used in eye drops or ointment to
treat bacterial conjunctivitis.
