Adverse drug reaction
From IDWiki
Background
Risk Factors
- Extremes of ages (elderly and young)
- Polypharmacy
- Pregnancy
- Breastfeeding
- Genetic factors
- e.g. specific genes predispose to AG ototoxicity
- Comorbidities, including renal and hepatic dysfunction
- Antimicrobials are one of the largest causes of adverse drug reactions
Immune-mediated Hypersensitivity Reactions
| Type | Description | Examples |
|---|---|---|
| I | immediate IgE-mediated reaction | anaphylaxis |
| II | antibody-mediated cytotoxic reaction | hemolytic anemia from penicillin |
| III | immune complex-mediated reaction | serum sickness from cephalosporins |
| IV | delayed cell-mediated reaction | DRESS |
| IVa | delayed Th1-mediated reaction | |
| IVb | delayed Th2-mediated reaction | |
| IVc | delayed CD8 T-cell-mediated reaction | |
| IVd | delayed T-cell-mediated neutrophilic reaction |
Non-immune-mediated Hypersensitivity Reactions
| Type | Description | Examples |
|---|---|---|
| Type A | Understood pharmacologic effects | serotonin syndrome from linezolid, thrush after antibiotics, drug toxicities, drug-drug interactions |
| Type B | Idiosyncratic | |
| Type C | Chronic effects | |
| Type D | Delayed effects, including carcinogenic or teratogenic |
Major Examples
Fluoroquinolones
- CNS: dizziness, HA, sleep disturbance, hallucinations, seizures, depression, peripheral neuropathy (3%)
- Seizures, especially with concomitant NSAIDs or theophylline due to GABA binding and NMDA activation
- Cipro worst culprit
- Seizures, especially with concomitant NSAIDs or theophylline due to GABA binding and NMDA activation
- QT prolongation
- Tendon rupture
- 90% was Achilles tendon; 50% bilateral
- Cipro caused 90% of cases
- Risk persists for up to a year
- Most cases resolve after discontinuation
- Risk factors: elderly, concomitant steroids, renal failure, diabetes, history of MSK disorders, male sex
- Steroids cause chondrocyte apoptosis
Beta Lactams
- Seizures
- Inhibits GABA release
- More common with renal failure, elderly, high doses
- 1 to 10 days after starting the abx
- Resolves 2 to 7 days after stopping
Metronidazole
- Peripheral neuropathy
- Usually reversible but takes time
- Starts after 4 weeks or 42 grams
- Free radicals causing nerve damage, and metronidazole causes degeneration
- Resolves in 2 to 24 weeks
Nitrofurantoin
- Pulmonary fibrosis
- May be acute or chronic (9 days vs months or years)
- No fevers, eosinophilia, or pleural effusions
- Risk factosr include CKD, high prolonged doses, older age, female sex
- Mechanism is toxic metabolites induce injury of lung microsomes with oxidative stress
- Acute: Type I or III hypersensitivity, resolves with discontinuation
- Chronic: cell-mediated or toxic response, fibrosis is irreversible
Drug Fevers
- Most commonly beta lactams and Septra
- Caused by byproducts of hepatically created metabolites?
- Can be high fevers; relative bradycardia, patient appears well, no rigors, maybe liver enzymes up, normal eosinophils, often left shift of elevated WBC
- Usually takes 5 to 10 days
- Normalizes withing 72 hours of discontinuation
QT Prolongation
- Risk factors include electrolyte abnormalities, age, female sex, structural heart disease, bradycardia, hypothyroidism, CNS process, obesity, genetics, alcohol and cocaine use
- Potassium wasting diuretics
- Antiarrhythmics
- Drug-drug interactions
- Higher dose
- Route of drug (IV > PO)
- EMA paper QT prolongation
- Concern if the drug causes 30-60 ms increase
- Clear concern if QTc >500 ms or increases by >60 ms
- Check repeat ECG at 3 to 5 days
Diarrhea
- Antibiotics are 25% of drug-induced diarrhea
- Appears within days, resolves after discontinuing
- Mechanism includes diruption of normal gut flora, which can also cause impaired fermentation
- Highest risk includes macrolides (promotility), fluroquinolones, amoxicillin/clavulatate
Acute Tubular Necrosis
- Aminoglycosides
- Vancomycin
- Inter
Interstitial Nephritis
- Typically beta lactams
- Oliguria, malaise, anorexisa, nausea/vomiting
- Rash, fever, eosinophils, arthralgias
- T-cell mediated hypersensitivity
- Reversible over weeks
- Should probably avoid the whole class of antibiotics
Rash
- Amipicillin is the msot common penicillin, more commoly in women, especially with viral infections
- Maculopapular rash
- Most common
- Not immediate (>1 hour after dose)
- Mechanism is T-cell mediated
Neutropenia/Thrombocytopenia
- From beta lactams
- Can either be from induced antibody formation against wthe bloodline with immune complex formation; can also have a direct marrow effect
- Anemia is rare, but can get autoimmune hemolytic anemia
- At least 10 days of penicillin before you see bone marrow suppression
- Start to recover after 3 to 4 days of discontinuation if it was marrow suppression
- Longer if immune-mediated reaction
- Linezolid, vancomycin,
Aplastic anemia
- From Septra
Daptomycin
- Asymptomatic CK rise:
- 8/8 patients in one case series were able to resume with normalized CK by withholding a dose and resuming 24 h later
