ADRs and Toxicity Flashcards
ADRs: Type A Reaction**
Dose-dependent to the known pharmacologic properties of the drug, most common
-Ex. orthostatic hypotension w/ doxazosin, nephrotoxocity w/ aminogylcosides, tachycardia w/ albuterol
ADRs: Type B Reaction**
NOT dose-dependent and unrelated to pharmacologic actions of drug and can be influenced by patient-specific factors
-Can occur with active or inactive ingredient
-Categorized further as immediate (within 60 minutes of exposure) or delayed (occurring days-months after exposure)
-Ex. drug allergies (typically NOT hereditary), hypersensitivity rxns, idiosyncratic rxns (from genetic differences such as G6PD deficiency)
Drug Allergies: Type I**
Immediate - within 15-30 minutes of drug exposure
-IgE mediated, ranging from minor local to severe systemic (ex. urticaria, bronchospasms, angioedema, anaphylaxis)
Drug Allergies: Type II**
Delayed - minutes to hours after drug exposure
-Antibody-mediated, usually occurring 5-8 days after exposure
-Ex. hemolytic anemia, thrombocytopenia
Drug Allergies: Type III**
Delayed - occur 3-10 hours after drug exposure
-Immune-complex reactions, occurring >/=1 week after exposure
-Ex. serum sickness
Drug Allergies: Type IV**
Delayed - occur 48 hours to weeks after drug exposure
-T cell-mediated
-Ex. SJS
Allergy vs. Intolerance: How to determine**
Gather Information:
1. What reaction occurred (ex. mild rash, severe rash w/ blisters, trouble breathing)?
2. When did it occur? About how old were you?
3. Can you use a similar drug in the class?
4. Do you have any food allergies or latex allergies?
Confusions with allergies:
-Stomach upset or nausea in absence of other hypersenstivity symptoms often incorrectly reported as allergy
-Non-immune drug hypersensitivity rxns: vancomycin when infused too rapidly can release histamine, opioids can cause non IgE-mediated release of histamine causing itching and hives
General Allergy Management**
Antihistamines: itching, swelling, and rash
NSAIDs, steroids: can sometimes be used for swelling
Epinephrine: to reverse bronchoconstriction
Drugs that cause photosensitivity (Type IV Hypersensitivity): limit sun exposure and recommend sunscreen**
Anti-microbials: quinolones, tetracyclines, voriconazole
Sulfa drugs
Others: amiodarone, diuretics (thiazide and loop), methotrexate, PO and topical retinoids, St. John’s Wort, tacrolimus
Define the following skin reactions: papule, macules, purpura, petechiae, ecchymosis, hematoma**
Papule: raised spots
Macule: flat spots
Purpura: red/purple skin spots (lesions) due to bleeding underneath skin which includes small and large spots
Petechiae: pinpoint in size (<3mm)
Ecchymosis: large bruised area (>5mm)
Hematoma: collection of blood under skin due to trauma to blood vessel, resulting in blood leaking into surrounding tissue (drugs that can cause: heparin, LMWH< other anticoagulants, phytonadione = vitamin K if given mistakenly as IM)
Define thrombotic thrombocytopenic purpura (TTP). What drugs can cause TTP?
“Drug-induced thrombotic microangiopathy” (DITMA) which is a blood disorder that clots form throughout the body and can consume PLTs, leading to bruising under the skin and formatoin of purpura (burises) and petechiae (dots) on skin
Drugs that can cause: oral P2Y12 inhibitors (ex. clopidogrel), sulfamethoxazole
Severe Cutaneous Adverse Reactions (SCARs):
-Types
-General Management
Types:
-Steven-Johnson Syndrome (SJS) and Toxic Epidermal Necrolysis (TEN): involve epidermal detachmentand skin loss generally occurring over 1-3 weeks after drug exposure which can result in severe mucosal erosions, a high body temperature, major fluid loss, and organ damage
-Drug reaction with eosinophilia and systemic symptoms (DRESS): includes a variety of skin eruptions accompanied by systemic rxns (fever, hepatic dysfunction, renal dysfunction, lymphadenopathy), but rarely involves mucosal surface
General TX:
-SJS/TEN: D/C offending agent ASAP, replace fluids and electrolytes, wound care, and administer pain medications; systemic steroids controveral in SJS and CI in TEN
-DRESS: D/C offending agent
Drugs associated with Severe Cutaneous Adverse Reactions (SCARS)**
Allopurinol, amoxicillin, ampicillin, carbamazepine, ethosuximide, lamotrigine, nevirapine, phenytoin, sulfamethoxazole, sulfasalazine, vancomycin
Anaphylaxis:
1. Severe, life-threatening allergic reaction that usually happens within ________ of drug exposure.
- S/Sx of anaphylaxis
- Treatment
- 1 hour
- Generalized uticaria (hives), swelling of mouth and throat, difficulty breathing or wheezing sounds, severe GI symptoms (ex. repetitive vomiting, severe abdominal cramping), and/or hypotension (dizziness, lightheadedness, loss of consciousness)
- -Call 911
-Typical TX: epinephrine injection + diphenhydramine + steroids +/- IV fluids
-DO NOT give any medications under head or in mouth to avoid airway obstruction
-Hx of anaphylaxis: carry a single-use epinephrine auto-injector (EpiPen, EpiPen Jr, Auvi-Q) –> generally available as 1mg/mL (previously labeled as 1:1000) in doses of 0.3mg (adults) and 0.15mg (pediatrics); emergency kit should consist of contact information, diphenhydramine tablets (25mg x2) if NO tongue/lip swelling
Epinephrine Counseling
ALL auto-injectors:
-Normal to see liquid remaining in device after injecting
-Call for emergency help because additional care may be needed
-A second dose in opposite leg may be give if needed prior to arrival of medical help
-Refrigeration NOT required
-All products can be injected through clothing
-Check the device periodically to make sure the medication is clear and NOT expired
-Tell family, caregivers, and others where pen is kept and how to use
EpiPen Administration:
-Remove from the carrying case and pull off blue safety release.
-Keep thumb, fingers, and hand away from orange (needle) end of device
-To inject, jab the orange end into the middle of outer thigh at a 90 degree angle
-Hold the needle firmly in place while counting to three
-Remove the needle and massage the area for ten seconds
-After injection, the orange tip will extend to cover the needle (if visible, should NOT be reused)
Symjepi: Pull off the cap, holding the syringe with the fingers. Inject in the middle of outer thigh, hold needle firmly in place for two seconds, then massage area for 10 seconds. After injection, slide the safety guard out over the needle.
Auvi-Q: Pull off the outer case, then follow the voice instructions to administer. Hold the needle firmly in place on the thigh for five seconds.
While cross-reactivity between cephalosporins and carbapenems to penicillins, on the NAPLEX, beta-lactams should be avoided. A notable exception is in ____________ where __________ can be used in a non-severe pencillin allergy.**
Acute otitis media; 2nd or 3rd gen cephalosporin
_________ is an antibiotic considered safe in penicillin allergy.**
Aztreonam
How to determine a true penicillin allergy.**
For immediate-type reactions (ex. anaphylaxis), a skin test can assess risk:
-Pts with negative result should be given an PO drug “challenge” dose before full dose TX
-Pts with positive result should avoid use of drug
-Should NOT be performed if hx of severe cutaneous rxns (SJS/TEN)
-Many cephalosporins can be safely tolerated in pts w/ mild PCN allergy
When would desensitization of a pencillin allergy be considered? Is densensitization a cure for the allergy?**
Penicillin is the ONLY acceptable treatment in pregnant or non-adherent pts with syphilis. If skin test positive, temporarily desensitize and admnister PCN.
-Densensitization: NOT a cure, only temporarily allows pt to receive medication, if dose missed, drug-free period allows immune system to re-sensitize
Drugs commonly associated with allergic rxns
- Beta-lactams**
- Sulfa drugs - most common in sulfamethoxazole (in Bactrim), other drugs should be avoided including sulfasalazine and sulfadiazine
-Package labeling for “non-arylamine” sulfonamides (ex. thiazide direutics, loop diuretics except ethacrynic acid, sulfonylureas, acetazolamide, zonisamide, celecoxib, cidofovir, darunavir, foasmprenavir, tipranavir) contain warnings/CIs for sulfa allergy (in-practice, low risk, but watch on NAPLEX)
-Sulfite or sulfate allergies do NOT cross-reaction with sulfonamides - Opioids - common hypersensitivity rxn with histamine release, but true allergy uncommon
- Heparin - watch for heparin-induced thrombocytopenia (HIT)
- Biologics - hypersensitivity rxns (ex. rituximab)
- ASA/NSAIDs - hypersensitivity rxns (most common: respiratory such as asthma or rhinorrhea and urticaria/angioedema)
- Radiocontrast media - immediate and delayed hypersensitivity rxns
________ and _______ foods are in the same family and can have cross-reactivity.**
Soy and Peanut
________, ________, and ______ are drugs CI in soy allergy.**
Clevidipine, propofol, Prometrium
_________, _________, and __________ are CI in egg allergy.**
Clevidipine, propofol, yellow fever vaccine
What are vaccine considerations with egg allergies?**
Even in severe egg allergy, can receive any inactivated flu vaccine
-Egg-free options: Flublok, Flucelvax
-In severe reaction to influenza vaccine, should NOT receive further doses of ANY influenza vaccine
CI in egg allergy: Yellow Fever
Assessing Causality of An Adverse Drug Reaction: Naranjo Scale
**ONLY for understanding brief considerations of assessment
- Are there previous conclusive reports on reaction?
- Did the adverse event apear after the suspected drug was given?
- Did the adverse reaction improve when the drug was D/C or a specific antagonist was given?
- Did the adverse reaction appear when the drug was readministered?
- Are there alternative causes that could (on their own) have caused the reaction?
- Did the reaction reappear when a placebo was given?
- Was the drug detected in any body fluid in toxic concentrations?
- Was the reaction more severe when dose increased or less severe when dose decreased?
- Did the pt have a similar rxn to same or similar drugs in any previous exposure?
- Was the adverse event confirmed by any objective evidence?
Yes to most questions = 1 point (2 points for #2 and #4)
-Score of >/=9 = definite ADR
-Score of 5-8 = probable ADR
-Score of 1-4 = possible ADR
-Score of 0 = doubtful ADR
Side effects, adverse events, and allergies can be reported to __________________ also known as _________. When drugs The FDA can require phase ____ trials for post-marketing safety surveillance programs for approved drugs and biologics. If the FDA receives enough reports that a drug is linked to a particular problem, the manufacturer may be required to do what? **
FDA Adverse Event Reporting System (FAERs); FDA MedWatch program; phase IV
-Manufacturers can be required to: update package insert, issue drug safety alerts to prescribers
What are the differences between warnings/precautions vs. contraindications vs. BBWs? **
Warnings/precautions: serious reactions that can result in death, hospitalization, medical intervention, disability, or teratogenicity –> may or may NOT change a prescribing decision
CI: drug CANNOT be used in that pt (risk outweights possible benefit)
BBW: risk of death or permanent disability from drug
What are REMS programs and medication guides?
REMS: Risk Evaluation and Mitigation Strategies –> can be required by FDA or developed by manufacturer and approved by FDA to ensure the benefits of a drug outweigh the risks (can include: medication guide, PPI, communication plan, elements to assure safe use or implement system)
Medication guides: FDA-approved patient handouts that detail important adverse event; if medication has a MedGuide, must be dispensed w/ original Rx and each refill (exception: hospitalized) –> can be required for drug or entire class of medications (ex. anticonvulsants, antidepressants, long-acting opioids, NSAIDs, ADHD stimulants)
Children are the most common victims of accidental poisoning. What is a measure to prevent this? What are other methods to prevent accidental poisonings children or not?
Child-resistant (C-R) packaging
-Most prescription drugs require C-R packaging (there are some exceptions ex. SL nitroglycerin)
-OTC drugs that require C-R packaging: diphenhydramine, iron, APAP, salicylates, NSAIDs, and drugs that have switched from Rx to OTC status
Other methods: unit dose, card adherence and safety packaging
First aid for poisonings: what should be done for topical, ocular, and oral ingestion?**
ALL: contact national poison control hotline
Topical: remove contaminated clothing and wash skin w/ soap and water for at least 15 minutes
Ocular: remove contact lenses, rinse eyes w/ gentle stream of water for at least 15 minutes
Oral: remove any remaining substances from mouth (if any symptoms of burning or irritation: drink a small amount of water or milk immediately)
What should be done for ingestion of button batteries?
Give 2 teaspoons of honey Q10 minutes while seeking immediate medical care –> ingestion can be fata within hours and honey or sucralfate can slow damage to esophagus and airway
_______ syrup was used previously to induce emesis for certain exposures, but is no longer commercially available or recommended. **
Ipecac syrup
Charcoal:
1. Activated charcoal is available OTC for ____________, but in the emergency room is approved for overdose of certain orally ingested drugs or chemicals.
- It is recommended to give activated charcoal within _________ of ingestion to absorb the drug. The dose is _________ with typically only one dose given.
- Prior to using activated charcoal, what should be considered?
- Gas/bloating, odor control –> OTC not recommended for overdose
- 1 hour; 1g/kg
- The airway should be protected to prevent aspiration (some ingested compounds can increase risk of aspiration - ex. hydrocarbons)
-CI: when airway is unprotected (ex. pt is unconscious, cannot clear their throat, cannot hold their head upright), with intestinal obstruction, when GI tract is NOT intact or when there is decreased peristalsis
Acetaminophen overdose:
1. Explain the metabolism of APAP and how overdose occurs
- Overdose of APAP leads to _____________ and doses should be limited to <_________mg/day to reduce this risk.
Acetaminophen can be metabolized into non-toxic metabolites via conjugation or at high doses, toxic metabolites (NAPQI) via CYP3E1. When toxic metabolites are made, glutathione-S-transferase (GSH) can convert this into non-toxic metabolites, but too many toxic metabolites can deplete this process leading to overdose
- Hepatotoxicity; 4000mg
Acetaminophen overdose: Explain the four phases of overdose including presentation and timeframe from ingestion.
Phase I (1-24 hours): commonly asymptomatic or non-specific symptoms (ex. N/V)
Phase II (24-72 hours): hepatotoxicity evident on labs (ex. elevated INR, AST/ALT), any symptoms from phase I usually subside
Phase III (72-96 hours): fulminant hepatic failure (jaundice, coagulopathy, renal failure, and/or death); irreversible damage at this point
Phase IV (>96 hours): the patient recovers or receives a liver transplant
Acetaminophen overdose: TX
To prevent hepatotoxicity, N-acetylcysteine (NAC) given quickly (ideally within 8 hours)
-MOA of NAC: free redical scavenger and precursor to glutathione (GSH) to increase GSH levels and convert NAPQI to non-toxic metabolites
-APAP levels are drawn and plotted on Rumack-Matthew nanogram to determine risk of hepatotoxicity (if possible or probable hepatotoxicity, give NAC)
-PO NAC (using injectable or inhalation solution): high dose given once then lower dose for 17 doses. Repeat dose if emesis occurs within 1 hour of administration
-IV NAC: three infusions over a total of 21 hours
Symptoms and antidote for: anticholinergic overdose**
Anticholinergics (ex. diphenhydramine, scopolamine, Atropa Belladonna):
-Symptoms: flushing, dry skin/mucous membranes, mydriasis (large pupils) with double or blurry vision, altered mental status, fever
-TX: primarily supportive care, rarely physostigmine given (inhibits acetylcholinesterase which breaks down ACh –> this increases ACh and decreases anticholingeric toxicity
Symptoms and antidote for: anticoagulant overdose**
Anticoagulants: overdose = bleeding –> TX is agent specific
-Apixiban, rivaroxaban: andexanet alfa (Andexxa)
-Dabigatran: idarucizumab (Praxbind)
-Warfarin: phytonadione (vitamin K), prothrombin complex concentrate (ex. Kcentra)
-Heparin, LMWH: protamine
Symptoms and antidote for: antipsychotic overdose
Symptoms: seizures
TX: primarily supportive care
-Benztropine for dystonia
-BZDs for seizures
-Bicarbonate if QRS-interval widening
Antidote for: benzodiazepine (BZD) overdose
Flumenazil
-Can cause seizures when used in pts taking BZDs chronically
-Sometimes used for non-BZD hypnotic overdose such as zolpidem, but NOT chronically recommended)
Antidote for: beta-blockers and CCBs overdose
Supportive care
-Glucagon if unresponsive to supportive treatment
Refractory to glucagon: high-dose insulin w/ dextrose may be used
Lipid emulsion to enhance eliminiation of some lipophilic drugs
CCBs: same as beta-blockers + IV calcium (chloride or gluconate) - avoid fast infusion, monitor ECG, do NOT infuse in same line as phosphate-containing solutions
Antidote for: cyanide (smoke inhalation, nitroprusside in high doses/long durations/renal impairment) overdose
hydroxocobalamin (Cyanokit), sodium thiosulfate + sodium nitrate (Nithiodote)
Antidote for: digoxin (oleander, foxglove) overdose
Digoxin immune Fab (DigiFab)
-Each DigiFab 40mg vial binds about 0.5mg digoxin; when amount unknonw, max adult dose is 20 vials
-Interferes with digoxin levels drawn after it has been given
Antidote for: ethanol (alcohol drinks)**
-What lab can this affect? **
Lab: can increase anion gap
TX: if chronic alcohol use suspected, thiamine (vitamin B1) to prevent Wernicke’s encephalopathy
Antidote for: 5-flurouracil (5-FU) and capecitabine overdose**
uridine triacetate (Vistogard)
What is the consideration in hydrocarbon (petrolatum products, gasoline, kerosene, mineral oil, paint thinners) overdose**
do NOT induce vomiting –> keep pt NPO due to aspiration risk
Antidote for: insulin or hypoglycemic overdose**
Dextrose injection or infustion, oral glucose (do NOT administer if pt is unconscious)
-If IV dextrose cannot be given: glucagon
-Sulfonylurea-induced hypoglycemia: octreotide (Sandostatin)
Symptoms and antidote for: isoniazid overdose
Symptoms: seizures, altered mental status
TX: IV pyridoxine (vitamin B6) and BZDs(
Antidote for: iron or aluminum overdose**
deferoxamine (Desferal)
-Iron overload from blood transfusions: deferiprone (Ferriprox) or deferasirox
Antidote for: methotrexate overdose**
IV sodium bicarbonate (to alkalinize urine)
Leucovorin (reduced form of folic acid) or levoleucovorin: rescue therapy after high-dose cancer TX
Glucarpidase (Voraxaze): rapidly lowers MTX levels in pts w/ AKI and delayed clearance
Methemoglobinemia:
-Occurs from overdose in what drugs?
-TX
-CI to TX
Overdose from: topical benzocaine (ex. OraGel or teething products), dapsone, nitrates, or sulonamides
TX: methylene blue (ProvaBlue)
-CI: G6PD deficiency; Avoid use with SSRIs and SNRIs (risk of serotonin syndrome)
Antidote for: neostigmine or pyridostigmine overdose
Pralidoxime (Protopam) - counteracts w/ muscle weakness and/or respiratory depression secondary due to overdose of acetylcholinesterase inhibitors to treat myasthenia gravis
-Atropine or glycopyrrolate can be given to prevent bradycardia from neostigmine
Nicotine overdose:
-Early symptoms
-Later symptoms
-TX
Early symptoms: abdominal pain, nausea, diaphoresis, tachycardia, tremors
Later symptoms: bradycardia, dyspnea, lethargy, coma, seizures
TX: supportive care (atropine for symptomatic bradycardia, BZDs for seizures)
Organophosphates (OP) overdose:
-OP agents
-Symptoms
-TX
OPs: insecticides (ex. malathion), nerve gases (ex. sarin)
Symptoms: SLUDD (Salivation, Lacrimatoin, Urination, Diarrhea, Defecation)
TX:
-Atropine: anticholinergic to reduce SLUDD symptoms
-Pralidoxime (Protopam): treats muscle weakness and relieves paralaysis of respiratory muscles by reactivating acetylcholinesterase
-Atropine and pralidoxime (DuoDate)
Antidote for: salicylate overdose**
Sodium bicarbonate to alkalinize urine to decrease drug reabsorption and increase excretion
Antidote for: stimulant (amphetamines) overdose**
BZDs for agitation or seizures
Antidote for: toxic alcohols (ex. ethylene glycol = antifreeze, diethylene glycol, methanol)
-What lab can this interfere with?**
Lab: can increase anion gap
TX: fomepizole preferred; ethanol if fomepizole unavailable
Antidote for: tricyclic antidepressant overdose
-Symptoms of overdose?**
-Symptoms: can cause fata arrhythmias
TX: sodium bicarbonate to decrease widened QRS complex, BZDs for agitatoin or seizures, vasopressors for hypotension
Overdose of valproic acid or topiramate leads to ___________ and ________ is the antidote.**
Hyperammonia; levocarnitine (Carnitor)
What are the possible actions to take in symptomatic treatment of overdose/poisoning when the substance taken is unknown or there are multiple substances? **
- Support circulation, airway, and breathing as impairments can be life-threatening
-Fluids, vasopressors for hypotension
-Atropine for bradycardia
-Mechanical ventilation for compromised airway
-Give naloxone if symptoms of pinpoint pupils and shallow breathing with somnolence - Treat seizures, severe agitatoin, or tachycardia with BZDs
- Treat hypoglycemia with oral carbohydrates (if pt alert), IV dextrose, or SC glucagon
- If an ECG demonstrates QT prolongation or QRS widening, administer sodium bicarbonate
- Check an APAP level and use the Rumack-Matthew nomogram to determine if NAC should be given
Antidotes for common bites and stings:
1. Mammal bites
- Black Widow spider bites
- Scorpion stings
- Snake bites (copperhead, cottonmouth, rattlesnake)
Mammal bites: Rabies vaccine (RabAvert, Imovax Rabies) + human rabies Immune globulin (HyperRAB S/D, Imogam Rabies-HT) - provides immediate antibodies while vaccine takes time to work
Black Widow: Antivenin for Latrodectus mactans
Scorpion: Antivenin immune Fab Centruoides (Anascorp)
Snake bites: Crotalidae polyvalent immune Fab (CroFab), Crotalidae Immune F(ab’)2 (Anavip)
