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.