Synthesis: Atlas of Pharmacoselection and Toxicology

A formulary is a dynamic decision-making tool at the point of care. The following table summarizes the critical drug selection and monitoring targets necessary to guide the prescription of the drugs detailed in this reference document.

File

Drug	Critical Molecular Target	Cardinal Toxicity to Monitor	Mandatory Organic Adjustment	High Risk Interaction
Paracetamol	Central Pool COX / TRPV1 / AM404	Centrilobular liver necrosis	Liver failure (avoid in severe cases)	Enzyme inducers (Rifampicin)
Metamizole	Central COX / peripheral NO-cGMP	Agranulocytosis / Arterial hypotension	Moderate-severe renal failure	Low-dose aspirin
Ibuprofen	Reversible COX-1 and COX-2 inhibition	GI bleeding / Renal papillary necrosis	Contraindicated if Cl_cr < 30 mL/min	Oral anticoagulants / Lithium
Ketorolac	Potent inhibition of COX-1 affinity	Massive GI bleeding / Acute renal failure	Contraindicated if Cl_cr < 45 mL/min	Other NSAIDs / Pentoxifylline
Celecoxib	Selective COX-2 inhibitor	Cardiovascular thrombotic events	Contraindicated if Cl_cr < 30 mL/min	CYP2D6 / Warfarin substrates
Morphine	µ opioid receptor agonism (MOP)	Respiratory depression / Neurotoxicity	Renal failure (avoid M3G/M6G)	CNS depressants (Benzodiazepines)
Tramadol	µ agonism / Inhibition of 5-HT and NE reassimilation	Generalized seizures / Serotonin syndrome	Reduce dose if Cl_cr < 30 mL/min	SSRIs / CYP2D6 inhibitors
Fentanyl	High potency µ receptor agonism	Respiratory depression / Chest in wood	Moderate-severe liver disease	CYP3A4 inhibitors (Clarithromycin)
Sumatriptan	5-HT receptor agonism_1B/1D	Coronary vasospasm / Chest tightness	Severe liver failure	Ergotamines / MAOI-A
Methotrexate	Inhibition of DHFR / AICAR Transformylase	Extreme myelosuppression / Interstitial pneumonitis	Contraindicated if Cl_cr < 30 mL/min	Trimethoprim-Sulfamethoxazole / NSAIDs
Leflunomide	Reversible inhibition of mitochondrial DHODH	Fulminant hepatotoxicity / Alopecia / Diarrhea	Avoid in decompensated cirrhosis	Methotrexate (hepatotoxic synergism)
Adalimumab	Functional blockade of soluble TNF-α/mTNF	Reactivation of Tuberculosis / Demyelination	Does not require systematic dose adjustment	Live attenuated vaccines
Tofacitinib	Selective JAK1 and JAK3 inhibitor	Herpes Zoster / Venous Thromboembolism	Reduce if Cl_cr < 30 or Child-Pugh B	CYP3A4 inhibitors / Live vaccines
Colchicine	Binding of cytoskeletal tubulin dimers	Hemorrhagic diarrhea / Neuromyopathy	Contraindicated if Cl_cr < 30 prophylactic	P-gp inhibitors (Clarithromycin)
Allopurinol	Suicidal inhibitor

Therapeutic Selection Summary

Three clinical questions resolve most risk scenarios in pain and rheumatology:

What is the patient's creatinine clearance? If the clearance is less than 30 mL/min, NSAIDs, methotrexate and allopurinol require mandatory withdrawal or replacement with selective hepatic clearance drugs (such as celecoxib with caution, fentanyl or febuxostat).
Is there a high cardiovascular or gastrointestinal risk? If the gastrointestinal risk is high, coxibs with simultaneous gastroprotection are preferred, but if the coronary atherothrombotic risk predominates, coxibs and non-selective NSAIDs should be avoided, preferring paracetamol, minor opioids or local infiltrations.
Has the correct prophylactic screening been carried out? The initiation of immunomodulators and major biologics should never omit the rigorous rule-out of latent tuberculosis (anti-TNF) and protective serum antibodies against hepatitis or vaccines before starting active treatment.

"The difference between a drug and a poison lies exclusively in the dose and the pathophysiological understanding of the patient who receives it." — Fundamental Clinical Axiom.

Epistemis is educational review material. It is not a medical device, does not diagnose or prescribe treatment, and does not replace formal medical training, current clinical guidelines, or professional clinical judgment.

PreviousAllopurinol

System: Pain, Inflammation and Rheumatology
Cluster: Quick Guide to Clinical Selection

Download Epistemis