Al-Bayan University

Pharmacy college
3rd stage
Lecture 9
Antibiotics
Dr.Khulood Saadoon

Metabolism inhibitors antibacterial drugs

1- Inhibitors of folic acid synthesis. Sulfonamides
(Sulfisoxazole, sulfadiazine, sulfadoxin)
2- Inhibitors of folic acid reduction
(Trimethoprim).
3- Inhibitors of folate synthesis and reduction
( Co- trimoxazole)
 Mechanism of action
• Folic acid is a coenzyme that responsible for DNA
synthesis in bacterial cells.
• These drugs inhibit synthesis or reduction of folic acid
by inhibition the enzymes responsible for these
processes.
• This leads to decrease synthesis of DNA in bacterial
cells., thus inhibit bacterial growth.
General properties of sulfonamides
• They are weak acidic drugs, they are classified according to
their pharmacokinetic properties.( duration of action and
absorption).
• Absorbable agents used orally and non-absorbable agents
used topically on skin or eye.
• They distribute well to all tissue and can pass BBB, placenta
and breast milk.
• They are highly bound to plasma proteins.
• They excreted in urine, the drug and metabolites precipitate
in urine causing stone formation ( crystalluria)
 Spectrum of activity
• They are bacteriostatic drugs.
• They act against G+ve and G-ve organisms
including E.coli, chlamydia, klebsiella, Nocardia)
also effective against protozoa and toxoplasma
gonadi.
• They are infrequently used as a single agent.
They are used in combination with other drugs
for treatment of malaria and toxoplasmosis.

Side effects and toxicity of sulfonamides

1- Hypersensitivity( rash, dermatitis, stevens-Johnson syndrome).
2- Gastrointestinal effects( nausea, vomiting, and diarrhea).
3-Hemolytic anemia in patient with G6PD deficiency
4- Crystalluria. Alkalinization of urine and adequate hydration prevents this
problem which is primarily in older patients.
5-Kernicterus: In newborns, sulfonamides will displace bilirubin from
albumin. The excess bilirubin penetrates the CNS and causes this condition.
So it is contraindicated in pregnant and nursing mothers.
6-have drug-drug interactions by displacement other drugs from PPB such as
warfarin and phenytoin
Resistance to sulfonamides may occur.
 Drug Action Main uses Main side effects

Sulfonamides(SMZ) Static, against Gm – UTI, RTI, toxoplasmosis, Crystalluria, Rash, Anemia

Sulfamethaxzole ve,Gm+ve, other Leishmaniosis, in patients with G6PD
bacteria and protozoa Conjunctivitis and deficiency, Nausea,
trachoma(topically) Kernicterus
PCP(fungal infection in (CRANK)
HIV patients that causes
pneumonia)
Trimethoprim(TMP) Static, against Gm -ve UTI, RTI, Prostatitis Megaloplastic anemia
because of folic acid
deficiency

Co-trimoxazole Cidal, against G-ve cocci, UTI, RTI, GIT infections, Skin reactions, GIT
(SMZ+ TMP) bacilli, and rods Genital infection disturbances,
megaloplastic anemia.

Metronidazole(flagyl)
It is widely used drug, it has these properties:
1- It is effective bactericidal drug(against anaerobic
bacteria and some parasites).
2- It distributes to all body tissues(CSF, saliva, seminal
and vaginal fluids & can cross placenta).
3- There are different cheap dosage forms (oral,
injection, topical).
How does the drug work in anaerobic bacteria

• Metronidazole has a nitro group in its structure that

receives electrons from ferredoxin( present in
anaerobic parasites) in a redox reaction. The resultant
compound will be active and binds both to protein
and DNA of bacterial or parasite cell and is cytotoxic.
• This reduction process only occur in anaerobics that
have the enzyme responsible for this reaction.

Mechanism of action of metronidazole

 Clinical uses
1- DOC (Drug of choice) in amebiasis(E.histolytica)
2- Giardiasis ( Giardia lambilia)
3- Septicemia &Brain abscesss.(clostridia)
4-Pseudomembranous colitis(c.difficle toxin).
5- Trichomonas vaginalis.
6- Effective against Anerobic infection caused by
B.fragllus)
7- peptic ulcer with other drugs against H.pylori.

Side effects
1- GIT disturbances(cramps, nausea and vomiting)
2- Unpleasant metallic taste.
3-Oral moniliasis.
4-Discoloration of urine( reddish-brown color).
5- CNS disturbances( dizziness, vertigo, numbness,
headache, seizure in patient with epilepsy).
Note: can be used in pregnant women in specific
conditions.
 Important side effects of antibiotics
Drug Main side effects
Penicillins & Hypersensitivity
cephalosporins
Aminoglycosides Nephrotoxicity, ototoxicity
(gentamicin)
Tetracyclines Teeth discoloration and bone deformity
Erythromycin GIT disturbances, liver toxicity
Sulfonamides CRANK
Metronidazole GIT disturbances, metallic taste, urine
discoloration

Main contraindications of antibiotics

Drug Reason
Infants Sulfonamides Kernicterus(brain damage)
Children Tetracyclines Bone deformity and teeth discoloration
( it binds with Ca)
Old Aminoglycosides Nephrotoxicity, ototoxicity
patients
Pregnancy Aminoglycosides, Deafness to infant
Tetracyclines, Teeth discoloration and bone deformity