Transcript 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.
ANAPHYLAXISTREATMENT

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
TrimethoprimSulfamethoxazole
DIHYDROPTEROIC ACID
Dihydropteroate Synthetase
DHF
Dihydrofolate Reductase
THF
FOLINIC ACID
DNA
TRIMETHOPRIM
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.
TDH 7 /90
ve s ci el
cho lni e
ace ty ltran s fe rase
AC h
AC h
AC h
A ce ty Cl oA + C h
h gi h a ffni ity
up take
AC h
AC h
Amino
Glycosides
AC h
AC h
recep to r
AC h
A c +C h
AC h es te ra se
td h
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
R
Macrolides
Prolong
QT Interval
T
P
Q
S
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
SULFONAMIDES
CRYSTALLINE
AGGREGATES,
HEMATURIA,
OBSTRUCTION
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, arthralgiamyalgia 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.