drug allergies and adverse drug reactions/toxicology

Type A reaction

• Dose dependent

• Related to known pharmacologic properties

• Most common

-Reaction caused by drug factors

EX: tachycardia with albuterol

Type B reaction

• Not-dose dependent

• Unrelated to pharmacologic actions

-Reaction caused by patient specific factors

-Immediate or delayed

EX: allergies, HSR, idoisyncratic rxns

Type I-IV drug allergies

• I: immediate, igE

• II: delayed (5- 8 days), antibody mediated

• III: delayed (≥1 week), immune complex mediated

• IV: delayed (48 hr - weeks), SJS

Key drugs that cause photosensitivty (10 studygal)

• Amiodarone

• Diuretics

• Methotrexate

• Oral & topical retinoids

• FQ

• St johns wort

• Sulfa drugs

• Tacrolimus

• Tetracyclines

• Voriconazole

Common drugs that cause TTP (2)

• P2Y12 inhibitors (Clopidogrel)

• Bactrim

What is TTP?

Thrombotic Thromcytopenic Purapura

• Blood disorder where clots form throughout the body leading to bruising and petechiae (dots)

T/F: Systemic steroids are contraindicated with TEN

True

Drugs causes SJS/TEN/DRESS (Severe cutaneous adverse reactions) (11 studygal)

• Allopurinol

• Amoxicillin

• Ampicillin

• CBZ

• Ethosuximide

• Lamotrigine

• Nevirapine

• Phenytoin

• Sulfamethoxazole

• Sulfasalazine

• Vancomycin

What is the epi conc for anaphylaxis?

1 mg/mL or 1:1000

Drugs to avoid in soy allergy (2)

• Propofol

• Clevidipine

Drugs to avoid with egg allergy (3)

• Propofol

• Clevidipine

• Yellow fever vaccine

What scale should be used to access causality of an ADR?

Naranjo scale

Where should ADR be reported?

• FAERS (FDA AE Reporting System) aka the FDA Medwatch program

Who develops REMS programs?

Manufacturer and approved by FDA ***

Scorpion sting antidote

Antivenin immune Fab Centuroides

Snake bite antidote

Crotalidae polyvalent immune Fab (CroFab)

Phases of APAP overdose (4)

• 1 (1-24hr): n/v

• 2 (24-72 hr): increased AST/ALT, INR

• 3 (72-96 hr): fulminant liver fx

• 4 (>96 hr): recovery or TXP

Organophosphate overdose SXS

SLUDD

Organophosphate overdose TX (2)

• Atropine

• Pralidoxime

emergency use authorization (EUA)

use of unapproved medications or unapproved indications for medications during a time of critical need

when to give activated charcoal for orally ingested drugs

within 1 hr

activated charcoal dose

1 g/kg

What must be done prior to giving activated charcoal

protect airway (CI if airway not protected)

what compounds increase risk of aspiration

hydrocarbons

Dose of acetaminophen that reduces risk

<4000 mg

What metabolizes APA to NAPQI

CYP450 2E1

APAP antidote

NAC (PO and IV)

Anticholinergics antidote

physostigmine

apixaban and rivaroxaban antidote

andexanet alfa (andexxa)

Dabigatran (pradaxa) antidote

Idarucizumab (Praxbind)

warfarin antidote

phytonadione (vitamin K)

prothrombin complex concentrate (Kcentra)

heparin and LMWH antidote

Protamine

antipsychotics antidote

Benztropine

BZDs antidote

Flumazenil

Beta blockers antidote

glucagon

CCB antidote

Calcium (IV)

Cyanide, nitroprusside antidote

Hydroxocobalamin (Cyanokit)

digoxin antidote

Digoxin immune Fab (Digibind)

Ethanol antidote

Thiamine (B1) to prevent Wernicke's encephalopathy

Can increase anion gap

5-FU, capecitabine antidote

uridine triacetate

Insulin antidote

IV dextrose or glucagon

Isoniazide antidote

IV pyridoxine (vitamin B6)

Iron antidote

Deferoxamine (Desferal)

Methotrexate antidote

Sodium bicarb (IV)

Leucovorin (folinic acid)

levoleucovorin (Fusilev)

Neostigmine, Pyridostigmine antidote

Pralidoxime

nicotine antidote

- Supportive care

- Atropine

organophosphates (OPs) including insecticides overdose tx

causes SLUDD

Atropine

Pralidoxime

Methemoglobinemia from topic benzocaine

methylene blue (CI in G6PD deficiency)

salicylates antidote

sodium bicarbonate

Stimulants antidote

benzos

Toxic alcohols antidote

Fomepizole

TCAs antidote

sodium bicarbonate

Valproic acid or topiramate induced hyperammonemia antidote

levocarnitine

SLUDD

salivation, lacrimation, urination, digestion, defecation

Mammal bites antidote

rabies

Drugs that can cause sulfa allergy reaction

sulfamethoxazole

sulfasalazine

sulfadiazine

Thiazide diuretics

Loop diuretics

sulfonylureas

acetazolamide

zonisamide

celecoxib

darunavir

Do sulfite or sulfate cross react with sulfonamides

no

If allergic to penicilin can you use cephalosporin

no

Ex: when to use desensitization

pregnant pt has syphilis and penicillin allergy