SIDE EFFECTS AND TOXICITY

GI EFFECTS Almost all antibiotics are irritating to the GI tract. Diarrhea is very common. Nausea, vomiting.

TETRACYCLINES-GI EFFECTS Common upon oral administration. Epigastric burning and distress, abdominal discomfort, nausea and vomiting and diarrhea.

ADVERSE EFFECTS Nausea and vomiting usually subside as medication continues. If troublesome GI irritation can be controlled with food. Important to distinguish irritative diarrhea from superinfection.

CLINDAMYCIN Diarrhea fairly common

HYPERSENSITIVITY REACTIONS Most antibiotics produce hypersensitivity reactions. β-lactams. Sulfonamides and its combinations.

PENICILLINS Cross allergenicity among all the penicillins (and other beta lactams). Results from a previous treatment.

HYPERSENSITIVITY REACTIONS Occurs with almost any dosage form of penicillin. Oral penicillins have a lower risk than parenterals. Usually clear with elimination of the penicillin.

HYPERSENSITIVITY REACTIONS Skin rashes. Fever. Bronchospasm. Vasculitis, serum sickness, exfoliative dermatitis, contact sensitivity, local swelling and redness,oral lesions, eosinophilia. ANGIOEDEMA AND ANAPHYLAXIS.

ANAPHYLAXIS Most important immediate danger. Incidence is low ( %). Sudden, severe hypotension and rapid death.

ANAPHYLAXIS Careful observation of the patient is important.

ANAPHYLAXIS- TREATMENT Epinephrine (IV or IM) IV steroids Supportive measures

MGMT. OF THE PATIENT POTENTIALLY ALLERGIC Evaluation and history.

Depts/ ENT

DESENSITIZATION.

CEPHALOSPORINS Rashes occur frequently. Cross-sensitivity to penicillins.

HYPERSENSITIVITY REACTIONS Patients with a history of a mild or temporally distant reaction to penicillin appear to be at low risk.

Sulfonamides Skin rashes are common.

STEVENS JOHNSON SYNDROME Uncommon but most likely to occur following sulfonamide therapy

PHOTOSENSITIVITY Sulfonamides Tetracyclines Fluoroquinolones

HEMATOLOGICAL TOXICITY Sulfonamides (with trimethoprim) Chloramphenicol Ticarcillin and Piperacillin Linezolid

Trimethoprim- Sulfamethoxazole

HEMATOLOGICAL EFFECTS Leukopenia, thrombocytopenia and megaloblastosis. Most likely in patients with preexisting folate deficiency or in patients taking prolonged therapy.

DIHYDROPTEROIC ACID TRIMETHOPRIM Dihydrofolate Reductase Dihydropteroate Synthetase DHF THF DNA FOLINIC ACID

CHLORAMPHENICOL HEMATOLOGICAL TOXICITY-2 TYPES

IDIOSYNCRATIC APLASTIC ANEMIA Leukopenia, thrombocytopenia, and aplasia of the marrow. Not dose-related. Can be fatal.

DOSE-DEPENDENT ANEMIA Reversible dose-related suppression of bone marrow. Usually presents as anemia, reticulocytopenia and increased serum iron. Associated with high doses and/or prolonged treatment. Results from inhibition of mitochondrial protein synthesis.

TICARCILLIN AND PIPERACILLIN Prolong bleeding time (by altering platelet function).

LINEZOLID` Myelosuppression (anemia, thrombocytopenia, leukopenia)

HEPATOTOXICITY Erythromycin estolate (cholestatic hepatitis) Tetracyclines

CHOLESTATIC HEPATITIS It is caused primarily by the estolate. Not dose-related. It is probably a hypersensitivity reaction (to estolate ester).

TETRACYCLINES Dose-related hepatotoxicity (pregnancy).

NEUROLOGICAL EFFECTS Imipenem (seizures) Aminoglycosides Fluoroquinolones Metronidazole

AMINOGLYCOSIDES

NEUROMUSCULAR BLOCKADE Rare but potentially serious. Occurs at high concentrations of aminoglycosides or in patients with an underlying risk factor. Acute neuromuscular blockade, respiratory paralysis and death can occur.

Amino Glycosides

FLUOROQUINOLONES CNS effects such as headache, restlessness, and dizziness. High doses may produce convulsions.

METRONIDAZOLE Headache, dizziness, peripheral neuropathy.

CARDIOVASCULAR EFFECTS Fluoroquinolones Erythromycin Chloramphenicol

FLUOROQUINOLONES Some 3 rd and 4 th generation FQ’s can prolong the QT interval.

His/Purk. Ventricle P R Q S T Prolong QT Interval Macrolides

Torsade de pointes - Polymorphic Ventricular Tachycardia Prolonged QT

CHLORAMPHENICOL

GRAY BABY SYNDROME Neonates, especially premature babies. Abdominal distention, vomiting, circulatory collapse, ashen or pallid cyanosis. Inadequate glucuronidation in the newborn.

NEPHROTOXICITY Sulfonamides Aminoglycosides Vancomycin

CRYSTALLINE AGGREGATES, HEMATURIA, OBSTRUCTION SULFONAMIDES

AMINOGLYCOSIDES

Accumulate in the renal cortex (mainly proximal tubules). Reversible and usually mild. Reduced excretion can lead to ototoxicity.

OTOTOXICITY Aminoglycosides Vancomycin

OTOTOXICITY The most serious toxic effect (uncommon, irreversible and cumulative). Caused by all the aminoglycosides.

OTOTOXICITY Both auditory and vestibular dysfunction can occur. Results from destruction of sensory hair cells.

OTOTOXICITY Several factors increase the risk. Careful monitoring is important.

EFFECTS ON BONE AND CARTILAGE Tetracyclines Fluoroquinolones

TETRACYCLINES

FLUOROQUINOLONES

EFFECTS ON TEETH Tetracyclines

INFUSION-RELATED EVENTS Vancomycin Streptogramins

RED NECK OR RED MAN SYNDROME Rapid IV infusion of vancomycin may cause erythematous or urticarial reactions, flushing, tachycardia and hypotension. Due to a direct toxic effect on mast cells (with histamine release).

STREPTOGRAMINS Pain at infusion site, arthralgia- myalgia syndrome.

SUPERINFECTIONS Broad spectrum penicillins and cephalosporins. Chloramphenicol Tetracyclines Clindamycin

CLINDAMYCIN-AAPC

AAPC Characterized by watery diarrhea, abdominal pain, fever, blood and mucus in stools. It can be fatal.

Clindamycin

Vancomycin and metronidazole

SULFONAMIDES Urinary tract disturbances -formation of crystalline aggregates in urinary tract, hematuria and obstruction. DRINK ADEQUATE FLUIDS. Less likely with the newer more soluble sulfonamides.