SIDE EFFECTS AND TOXICITY
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Transcript of SIDE EFFECTS AND TOXICITY
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 (0.04 -0.2%).
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.
www.bris.ac.uk/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
DIHYDROPTEROIC ACID
TRIMETHOPRIMDihydrofolate Reductase
Dihydropteroate Synthetase
DHF
THF
DNAFOLINIC 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.
ACh ACh
ACh
ACh
AChACh
ACh
Ac + Ch
cholineacetyltransferase
high affinityuptake
vesicle
receptorACh esterase
ACh
tdh
AcetylCoA + ChTD
H 7/
90
AminoGlycosides
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 3rd and 4th generation FQ’s can prolong the QT interval.
His/Purk.
Ventricle
P
R
QS
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
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.