Adverse drug reaction: Difference between revisions
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− | == |
+ | ==Risk Factors== |
− | * Extremes of ages (elderly and young) |
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− | * Polypharmacy |
||
− | * Pregnancy |
||
− | * Breastfeeding |
||
− | * Genetic factors |
||
− | ** Specific genes predispose to AG ototoxicity |
||
− | * Comorbidities, including renal and hepatic dysfunction |
||
− | * Antimicrobials are one of the largest causes of adverse drug reactions |
||
+ | *Extremes of ages (elderly and young) |
||
− | == Classification == |
||
+ | *[[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 |
||
+ | |||
+ | ==Classification== |
||
{| class="wikitable" |
{| class="wikitable" |
||
− | ! |
+ | !Type |
− | ! |
+ | !Description |
|- |
|- |
||
− | | |
+ | |Type A |
− | | |
+ | |Understood pharmacologic effects |
|- |
|- |
||
− | | |
+ | |Type B |
− | | |
+ | |Idiosyncratic |
|- |
|- |
||
− | | |
+ | |Type C |
− | | |
+ | |Chronic effects |
|- |
|- |
||
− | | |
+ | |Type D |
− | | |
+ | |Delayed effects, including carcinogenic or teratogenic |
|} |
|} |
||
− | == |
+ | ==Immunologic Hypersensitivity Reactions== |
{| class="wikitable" |
{| class="wikitable" |
||
− | ! |
+ | !Type |
− | ! |
+ | !Description |
+ | !Example |
||
|- |
|- |
||
− | | |
+ | |I |
− | | IgE-mediated |
+ | |immediate IgE-mediated reaction |
+ | |[[anaphylaxis]] |
||
|- |
|- |
||
− | | |
+ | |II |
+ | |antibody-mediated cytotoxic reaction |
||
− | | hemolytic anemia from PCN |
||
+ | |[[hemolytic anemia]] from [[penicillin]] |
||
|- |
|- |
||
− | | |
+ | |III |
+ | |immune complex-mediated reaction |
||
− | | Serum sickness from cephalosporings |
||
+ | |[[serum sickness]] from cephalosporins |
||
|- |
|- |
||
− | | |
+ | |IV |
+ | |delayed cell-mediated reaction |
||
− | | DRESS |
||
+ | |[[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-immunologic Reactions== |
− | === |
+ | ===Predictable=== |
− | * Pharmacologic side effect, eg serotonin syndrome from linezolid |
||
− | * secodary pharma side effect, eg. thrush after abx |
||
− | * drug toxicity |
||
− | * drug-drug interactions |
||
− | * .. |
||
− | * ... |
||
− | * .. |
||
+ | *Pharmacologic side effect, eg serotonin syndrome from linezolid |
||
− | === Non-predictable === |
||
+ | *secodary pharma side effect, eg. thrush after abx |
||
+ | *drug toxicity |
||
+ | *drug-drug interactions |
||
+ | *.. |
||
+ | *... |
||
+ | *.. |
||
+ | |||
+ | ===Non-predictable=== |
||
... |
... |
||
− | == |
+ | ==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 |
||
+ | *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 |
||
− | === Fluoroquinolones === |
||
+ | *Appears within days, resolves after discontinuing |
||
− | * CNS: dizziness, HA, sleep disturbance, hallucinations, seizures, depression, peripheral neuropathy (3%) |
||
+ | *Mechanism includes diruption of normal gut flora, which can also cause impaired fermentation |
||
− | ** Seizures, especially with concomitant NSAIDs or theophylline due to GABA binding and NMDA activation |
||
+ | *Highest risk includes macrolides (promotility), fluroquinolones, amoxicillin/clavulatate |
||
− | *** Cipro worst culprit |
||
− | * 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 |
||
− | ** |
||
− | === |
+ | ===Acute Tubular Necrosis=== |
− | * 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 |
||
+ | *Aminoglycosides |
||
− | === Metronidazole === |
||
+ | *Vancomycin |
||
− | * Peripheral neuropathy |
||
+ | *Inter |
||
− | ** 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 |
||
− | === |
+ | ===Interstitial Nephritis=== |
− | * 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 |
||
+ | *Typically beta lactams |
||
− | === Drug Fevers === |
||
+ | *Oliguria, malaise, anorexisa, nausea/vomiting |
||
− | * Most commonly beta lactams and Septra |
||
+ | *Rash, fever, eosinophils, arthralgias |
||
− | * Caused by byproducts of hepatically created metabolites? |
||
+ | *T-cell mediated hypersensitivity |
||
− | * Can be high fevers; relative bradycardia, patient appears well, no rigors, maybe liver enzymes up, normal eosinophils, often left shift of elevated WBC |
||
+ | *Reversible over weeks |
||
− | * Usually takes 5 to 10 days |
||
+ | *Should probably avoid the whole class of antibiotics |
||
− | * Normalizes withing 72 hours of discontinuation |
||
− | === |
+ | ===Rash=== |
− | * 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 |
||
+ | *Amipicillin is the msot common penicillin, more commoly in women, especially with viral infections |
||
− | === Diarrhea === |
||
+ | *Maculopapular rash |
||
− | * Antibiotics are 25% of drug-induced diarrhea |
||
+ | **Most common |
||
− | * Appears within days, resolves after discontinuing |
||
+ | **Not immediate (>1 hour after dose) |
||
− | * Mechanism includes diruption of normal gut flora, which can also cause impaired fermentation |
||
+ | **Mechanism is T-cell mediated |
||
− | * Highest risk includes macrolides (promotility), fluroquinolones, amoxicillin/clavulatate |
||
+ | ===Neutropenia/Thrombocytopenia=== |
||
− | === Acute Tubular Necrosis === |
||
− | * Aminoglycosides |
||
− | * Vancomycin |
||
− | * Inter |
||
+ | *From beta lactams |
||
− | === Interstitial Nephritis === |
||
+ | **Can either be from induced antibody formation against wthe bloodline with immune complex formation; can also have a direct marrow effect |
||
− | * Typically beta lactams |
||
+ | **Anemia is rare, but can get autoimmune hemolytic anemia |
||
− | * Oliguria, malaise, anorexisa, nausea/vomiting |
||
+ | **At least 10 days of penicillin before you see bone marrow suppression |
||
− | * Rash, fever, eosinophils, arthralgias |
||
+ | **Start to recover after 3 to 4 days of discontinuation if it was marrow suppression |
||
− | * T-cell mediated hypersensitivity |
||
+ | **Longer if immune-mediated reaction |
||
− | * Reversible over weeks |
||
+ | *Linezolid, vancomycin, |
||
− | * Should probably avoid the whole class of antibiotics |
||
− | === |
+ | ===Aplastic anemia=== |
− | * 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 |
||
+ | *From Septra |
||
− | === 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, |
||
− | === |
+ | ===Daptomycin=== |
− | * From Septra |
||
+ | *Asymptomatic CK rise: |
||
− | === Daptomycin === |
||
+ | **8/8 patients in one case series were able to resume with normalized CK by withholding a dose and resuming 24 h later |
||
− | * 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 |
||
− | == |
+ | ==List of Adverse Drug Reactions== |
− | === |
+ | ===Antibiotics=== |
{{#ask: |
{{#ask: |
||
[[Category:Antibiotics]] |
[[Category:Antibiotics]] |
||
|?Adverse drug reaction |
|?Adverse drug reaction |
||
}} |
}} |
||
− | === |
+ | ===Antifungals=== |
{{#ask: |
{{#ask: |
||
[[Category:Antifungals]] |
[[Category:Antifungals]] |
||
|?Adverse drug reaction |
|?Adverse drug reaction |
||
}} |
}} |
||
− | === |
+ | ===Antivirals=== |
{{#ask: |
{{#ask: |
||
[[Category:Antivirals]] |
[[Category:Antivirals]] |
Revision as of 19:45, 29 July 2020
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
Classification
Type | Description |
---|---|
Type A | Understood pharmacologic effects |
Type B | Idiosyncratic |
Type C | Chronic effects |
Type D | Delayed effects, including carcinogenic or teratogenic |
Immunologic Hypersensitivity Reactions
Type | Description | Example |
---|---|---|
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-immunologic Reactions
Predictable
- Pharmacologic side effect, eg serotonin syndrome from linezolid
- secodary pharma side effect, eg. thrush after abx
- drug toxicity
- drug-drug interactions
- ..
- ...
- ..
Non-predictable
...
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