High-Yield Pharmacotherapy & Adverse Reactions

Critical Antidotes & Reversal Agents

Toxin / Drug	Specific Antidote / Reversal Agent	Mechanism / Key Clinical Clue
Acetaminophen	N-Acetylcysteine (NAC)	Replenishes hepatic glutathione reserves. Check Rumack-Matthew nomogram at 4 hours.
Opioids	Naloxone	Competitive mu-opioid receptor antagonist. Monitor for resedation.
Benzodiazepines	Flumazenil	GABA-A competitive antagonist. Caution: Can precipitate acute seizures in chronic users.
Warfarin	4-Factor PCC + IV Vitamin K	4-Factor Prothrombin Complex Concentrate rapidly restores Factors II, VII, IX, X, Protein C & S.
Heparin / LMWH	Protamine Sulfate	Positively charged base binds negatively charged heparin molecules. Partial reversal for LMWH.
Direct Oral Anticoagulants (DOACs)	Idarucizumab (for Dabigatran); Andexanet alfa (for Apixaban/Rivaroxaban)	Specific antibody fragments / decoy factor Xa.
Beta-Blockers	Glucagon (+ High-Dose Insulin Euglycemia)	Bypasses beta-receptors to increase myocardial cAMP via Gs protein activation.
Calcium Channel Blockers	IV Calcium Gluconate + High-Dose Insulin	Promotes myocardial calcium influx and metabolic fuel utilization.
Digoxin	Digoxin-specific Fab fragments	Indicated for malignant arrhythmias, K+ > 5.0 mEq/L, or ingestions > 10 mg.
Tricyclic Antidepressants (TCAs)	IV Sodium Bicarbonate (NaHCO3)	Overcomes fast sodium channel blockade and alkalinizes serum to decrease active free drug.
Ethylene Glycol / Methanol	Fomepizole (or Ethanol)	Competitive inhibitor of alcohol dehydrogenase; prevents toxic metabolite generation.
Organophosphates (Cholinergic)	Atropine (first) + Pralidoxime (2-PAM)	Atropine reverses muscarinic hyperstimulation; 2-PAM regenerates acetylcholinesterase at nicotinic synapses.

Cytochrome P450 Interactions

Major CYP450 Inhibitors (Increase substrate levels → toxicity)

SICKFACES.COM: Sodium valproate, Isoniazid, Cimetidine, Ketoconazole (Azoles), Fluconazole, Alcohol (acute binge), Chloramphenicol, Erythromycin/Clarithromycin, Sulfonamides, Ciprofloxacin, Omeprazole, Metronidazole, Grapefruit juice.

Major CYP450 Inducers (Decrease substrate levels → therapeutic failure)

CRAP GPS: Carbamazepine, Rifampin, Alcohol (chronic), Phenobarbital, Griseofulvin, Phenytoin, St. John’s Wort.

See the full High-Yield Drug Interaction Lookup Matrix for searchable CYP450, P-gp, QT, and toxicity pairs with mechanism, consequence, and next step.

Step 1 Recall: Enzyme Deficiency Drug Traps

G6PD deficiency (X-linked): oxidative stress → Heinz bodies, bite cells, hemolysis. Triggers: primaquine, nitrofurantoin, TMP-SMX, dapsone, rasburicase, fava beans. Next step: stop the trigger, supportive care.
Pseudocholinesterase deficiency: prolonged apnea after succinylcholine (or mivacurium). Next step: ventilate until spontaneous recovery; dibucaine number confirms.

High-Yield Anticoagulant Principles & HIT Management

flowchart TD
    Heparin["Patient Receiving Heparin / LMWH"] --> Drop{"Platelet Count Drops >50% or Nadir <100k at Days 5-10?"}

    Drop -- "YES (Suspected HIT Type II)" --> Action1["1. STOP all Heparin products immediately"]
    Action1 --> Action2["2. Send PF4-Heparin ELISA + Serotonin Release Assay (SRA)"]
    Action2 --> Action3["3. Initiate non-heparin Direct Thrombin Inhibitor: ARGATROBAN or BIVALIRUDIN (or Fondaparinux)"]
    Action3 --> Avoid["AVOID:\n• Platelet transfusion (causes arterial 'white clot' thrombosis)\n• LMWH (100% cross-reactivity)\n• Early Warfarin (causes microvascular thrombosis & skin necrosis via Protein C depletion)"]

Antibiotic Selection Nuances in Special Populations

Clinical Presentation	First-Line Regimen	Major Drug Trap to AVOID
Community-Acquired Pneumonia in Pregnancy	Ceftriaxone + Azithromycin (or Amoxicillin-Clavulanate + Azithromycin)	Fluoroquinolones (cartilage toxicity / arthropathy) and Doxycycline (bone growth retardation, tooth discoloration).
*Domestic Cat Bite (Pasteurella multocida)*	Amoxicillin-Clavulanate (Augmentin)	Cephalexin, Ciprofloxacin, Clindamycin (lack adequate Pasteurella coverage).
Uncomplicated Cystitis in 1st Trimester Pregnancy	Nitrofurantoin, Cephalexin, or Fosfomycin	TMP-SMX (neural tube defect antifolate in 1st trimester; kernicterus in 3rd trimester) and Fluoroquinolones.
Acute Gout Flare with Severe Chronic Kidney Disease	Intra-articular Corticosteroid or Oral Prednisone	NSAIDs (Indomethacin) (precipitates acute renal failure) and Colchicine (neuromyopathy / toxicity with GFR < 30).