Health & Wellness

Types of Painkillers

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Updated:4/9/2026
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Drug Class
Examples
Mechanism
Best For
Key Risk
Known For
NSAIDs (non-selective)
Ibuprofen, naproxen, diclofenac, aspirinCOX-1/COX-2 inhibition, reduces prostaglandinsInflammatory pain, musculoskeletal, period painGI bleeding, kidney damage, cardiovascularMost widely used OTC painkillers globally, don't mask fever as well as acetaminophen
COX-2 Selective NSAIDs
Celecoxib (Celebrex), etoricoxibSelective COX-2 inhibitionArthritis pain in GI-sensitive patientsCardiovascular (Vioxx withdrawn in 2004)Developed to spare the stomach, Vioxx scandal is largest drug withdrawal in history
Acetaminophen (Paracetamol)
Tylenol, PanadolCentral COX inhibition (partially understood)Mild pain, fever, safe in pregnancyLiver toxicity in overdoseWorld's most used drug, overdose is leading cause of acute liver failure in the West
Weak Opioids
Codeine, tramadol, dihydrocodeineMu receptor agonist (weak) plus other effectsModerate pain after OTC failsAddiction, respiratory depression, serotonin syndrome (tramadol)Codeine metabolism varies genetically, tramadol has bizarre pharmacology beyond opioids
Strong Opioids
Morphine, oxycodone, hydromorphone, fentanylMu opioid receptor agonistSevere acute or cancer painAddiction, overdose, constipation, toleranceGold standard for severe pain, center of the opioid crisis, fentanyl 100x stronger than morphine
Gabapentinoids
Gabapentin, pregabalin (Lyrica)Alpha-2-delta calcium channel subunit bindingNeuropathic pain, fibromyalgia, postherpetic neuralgiaSedation, dependence, dizzinessOriginally antiepileptics, now massively prescribed off-label, emerging abuse concerns
Tricyclic Antidepressants
Amitriptyline, nortriptylineSerotonin/norepinephrine reuptake inhibitionChronic nerve pain, chronic headacheCardiac toxicity in overdose, anticholinergic effectsLow doses used for pain (much less than depression doses), helps sleep
SNRIs for pain
Duloxetine (Cymbalta), venlafaxineSerotonin/norepinephrine reuptake inhibitionDiabetic neuropathy, fibromyalgia, chronic back painDiscontinuation syndrome, nausea, sexual side effectsDuloxetine is FDA approved for multiple chronic pain conditions
Local Anesthetics
Lidocaine, bupivacaine, ropivacaineSodium channel blockade in nerve fibersProcedural pain, nerve blocks, postoperativeSystemic toxicity (LAST), cardiac arrestBasis of dental injections, epidurals, regional anesthesia
Topical Capsaicin
Capsaicin cream, Qutenza patchTRPV1 receptor desensitizationLocalized neuropathic pain, arthritisBurning sensation on applicationDerived from chili peppers, depletes substance P in nerve endings
Cannabinoids
Medical cannabis, nabiximols (Sativex)CB1/CB2 receptor modulationMS spasticity, cancer pain, neuropathic painCognitive effects, legal issues, dependenceIncreasingly accepted, strongest evidence in spasticity and chemo-induced nausea, not a magic bullet
Ketamine (low-dose)
IV ketamine, intranasalNMDA receptor antagonistRefractory chronic pain, acute severe painDissociation, bladder toxicity with chronic useOriginally an anesthetic, now used for depression and chronic pain in specialty clinics
Corticosteroids
Prednisone, dexamethasone, triamcinoloneAnti-inflammatory via gene regulationInflammatory flares, joint injectionLong-term: diabetes, osteoporosis, immunosuppressionNot true analgesics but reduce pain via inflammation, cortisone shots for joints
Muscle Relaxants
Cyclobenzaprine, baclofen, tizanidineCentral CNS depression or GABA-B agonismAcute muscle spasm, spasticitySedation, dependenceUsed for low back spasms, baclofen for MS, not as strong as advertised
Triptans
Sumatriptan, rizatriptan5-HT1B/1D receptor agonismAcute migraine attacksVasoconstriction, cardiac events in at-risk patientsGame-changer for migraine when introduced in 1990s, abort migraines rather than prevent them

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