Toxicity of anti-microbial drugs
Anti-microbial are those natural or synthetic drugs that are used to inhibit the action of microorganisms.
- Bacteriostatic agent :
– inhibit the growth and replication of microorganism
eg : tetracycline, sulfonamide, chloramphenical, erythromycin
- Bacteriocidal agent :
- Kills or irreversibly damage the microorganism
- Eg : penicillin, cephalosporin, aminoglycosides
Some primarly static drug become cidal at higher concentration
Eg : erythromycin, sulfonamide
Sulphonamide:
Sources:Sulphacetamide,Sulphadiazine,Mafedine,Sulphamethoxazole
Kinetics: All systemic acting sulphonamides are well absorbed from the gut.
They are bound to plasma proteins,particularly albumin.
Sulphonamides are distributed in almost all the tissues of the body including CSF. They cross placental barrier and reach foetal circulation.
They are metabolized in liver mainly by acetylation
Elimination occurs through urine,bile,faeces.sweat ,tear
Mechanism of action:They mainly act through the inhibition of folic acid synthesis which is necessary precursor of bacteria.
. The acetylated products of sulphonamides are poorly soluble in acidic urine and may cause crystalluria, haematuria or even obstruction to urinary tract .Leads to Renal damage.
Clinical Signs:
Renal failure or urinary tract infection Oliguria, haematuria, crystalluria and anuria.
Coagulation abnormalities due to inhibition of vitamin A
Keratoconjunctivitis siccs due to hypersensitivity reaction.
Diagnosis:
History , clinical signs
Decreased PCV due to anemia, leucopenia, urinalysis to detect crystalluria .
Treatment:
Fluid therapy in crystalluric patient .
Alkalanisation of urine by sodium carbonate.
Coagulation abnormalities can be corrected by Vit.K
Cyclosporine and policarpine for kerato-conjunctivitis
Prognosis: Depends on severity of renal damage.
Penicillins:
Mechanism of toxicity: Penicillin and all of the beta-lactam antibiotics exhibit antimicrobial activity by acting on the cell wall of bacteria. The beta-lactams inhibit the action of transpeptidases (penicillin-binding proteins) that form the bacterial cell wall. The mechanisms of toxicosis relate to hypersensitivity reactions, other immune-mediated reactions.
Immune-mediated hemolytic anemia is more commonly noted in horses given penicillin.
Penicillin induces bacterial overgrowth in the intestinal tract of guinea pigs with a resulting increase in production and absorption of bacterial exotoxins.
Clinical Signs: Clinical signs associated with an anaphylactic reaction may include hemorrhagic enterocolitis or respiratory distress.
Signs associated with immune-mediated hemolytic anemia include icterus, depression, pale mucous membranes, red-brown urine, splenomegaly, or tachycardia.
Procaine toxicosis is most commonly associated with excitement or loss of coordination.
Bacterial overgrowth in guinea pigs may result in acute death without other clinical signs.
Clinical Pathology. :Hemolytic anemia may be associated with decreased PCV and hemoglobin.
Treatment.: The treatment of anaphylaxis should focus on emergency and supportive care.
The animal’s airway should be maintained and oxygen provided, if necessary.
Epinephrine (0.5 to 1 ml of 1:10,000 dilution) may be necessary to maintain the vascular tone.
Fluid therapy may be necessary to provide sufficient volume for the cardiovascular system.
Immune-mediated hemolytic anemia also requires fluids and possibly transfusion.
Fluid therapy should be maintained to prevent hemoglobin-mediated damage to the renal tubules.
Prognosis:
. Acute anaphylaxis and hemolytic anemia are associated with a guarded prognosis.
Positive response to symptomatic and supportive therapy in the early phases of these diseases is encouraging.