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Local Anesthetics fail to provide adequate pain relief in acute inflammation.

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local anesthetics AND inflammation

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local anesthetics acute inflammation acidic tissue pH anesthetic failure mechanism

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In acute inflammation, local anesthetics are often less effective because inflamed tissue is acidic.
  • Local anesthetics are weak bases and exist as:
    • B: uncharged, lipid-soluble form that crosses the nerve membrane
    • BH⁺: charged form that blocks voltage-gated sodium channels from inside the neuron
  • In an acidic inflammatory environment, the equilibrium shifts toward the ionized BH⁺ form:
[ B + H^+ \rightleftharpoons BH^+ ]
  • Although BH⁺ is the form that binds the sodium channel, it cannot readily cross the lipid-rich nerve sheath and axonal membrane. Thus, too little uncharged B reaches the intracellular channel-binding site.
Result: delayed, weak, or failed nerve block, such as difficulty anesthetizing tissue around an abscess.
Other contributors include inflammatory sensitization of nociceptors, increased local blood flow that can remove drug from the site, and ongoing release of pain mediators.
An acidic environment is specifically described as antagonizing clinical local nerve block in Morgan and Mikhail's Clinical Anesthesiology, 7e, p. 486. The membrane-permeable uncharged form is required for onset, whereas the cationic form preferentially blocks sodium channels, as described in Goodman & Gilman’s The Pharmacological Basis of Therapeutics, p. 513.

Treatment of Hypertension.

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“Treatment of hypertension” is broad because the plan changes with blood-pressure severity, age, pregnancy, chronic kidney disease, diabetes, coronary disease, heart failure, and secondary causes.
  1. Confirming diagnosis and assessing cardiovascular risk
  2. Lifestyle treatment
  3. First-line drugs: ACE inhibitors/ARBs, calcium-channel blockers, thiazide-type diuretics
  4. Selecting initial single-drug vs combination therapy
  5. Treatment in key comorbidities and pregnancy
  6. Resistant hypertension and hypertensive emergencies
  7. Monitoring, adverse effects, and follow-up targets
In general, lifestyle measures are recommended for all patients. Most uncomplicated hypertension is treated with one or more of an ACE inhibitor or ARB, a long-acting dihydropyridine calcium-channel blocker, and a thiazide-like diuretic. Medication choice and blood-pressure target must be individualized, and acute severe hypertension requires a different approach.
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