Weak bases local anesthetics

Novocaine, which is used by dentists as a local anesthetic, is a weak base with pKh = 5.05. Blood has a pH of 7.4. What is the ratio of the concentration of novocaine to that of its conjugate acid in the bloodstream ... 

Local anesthetics are weak bases and are usually made available clinically as salts to increase solubility and stability. In the body, they exist either as the uncharged base or as a cation. The relative proportions of these two forms is governed by their pKa and the pH of the body fluids according to the Henderson-Hasselbalch equation ... 

Local anc.sthetics are normally weak bases (pK 8.S), which are only slightly soluble in water. Consequently, they arc usually marketed as aqueous solutions of their more soluble salts. Tbe.se solutions are often quite acidic, which makes them less prone to bacterial and fungal contaminatiun. However, an aqueous solution of the. salt of a local anesthetic will normally contain between 2 and 15% of the free base in equilibrium with the salt. 

Local anesthetics are weak bases and are usually made as HCl salts which are soluble and stable in water. The pK of the compound determines when the ionized and unionized forms are equal (see Table 1 for values of pK and percentage ionization at pH 7.4). The time of onset of the block is related to diffusion of the anesthetic into the nerve fiber, which occurs only in the unionized, or non-proton-ated form. Sodium bicarbonate is often added (1 mEq(lOml) lidocaine or 0.1 mEq(lOml) ... 

Answer B. Back to Basic Principles and the Henderson-Hasselbalch relationship. From the table, pH - pKa = -2.2. For a weak base, a value of -2 represents 1% nonionized, so in the present case the percentage of the local anesthetic in the nonionized form is <1%. Local anesthetics usually have reduced activity when injected into tissue that is septic because only a small fraction of the molecules are in the form capable of crossing biomembranes. Remember that this is not the form that interacts with the Na ion channel—that s the ionized form of the local anesthetic. 

EFFECT OF pH Local anesthetics tend to be only slightly soluble as unprotonated amines. Therefore, they generally are marketed as water-soluble salts, usually hydrochlorides. Since local anesthetics are weak bases (typical values range 8-9), their hydrochloride salts are mildly acidic. This property increases the stabdity of the local anesthetic esters and catecholamines added as vasoconstrictors. Following administration, the pH of the local anesthetic solution rapidly equilibrates to that of the extracellular fluids. 

I Local anesthetic (weak bases) infiltrate and anesthetize nerve bundles near sites of injection by I binding to inactive Na channels in their ionized forms. However, to get to the channel they must I diffuse though the lipid bilayer in an unionized form. Thus, their effects are influenced by pH. 

Local anesthetics bind preferentially to sodium channels in the open and inactivated states. Recovery from drug-induced block is 10-1000 times slower than recovery of channels from normal inactivation. Resting channels have a lower affinity for local anesthetics. The answer is (B). Since the drug is a weak base, it will be more ionized (protonated) at pH values lower than its pKjj. Since the pH given is 1 log unit lower (more acid) than the pK, the ratio of ionized to nonionized drug will be approximately 90 10. The answer is (D). (Recall from Chapter 1 that at a pH equal to pK, the ratio is 1 1 at 1 log unit difference, the ratio is [approximately] 90 10 at 2 units difference, 99 1 etc.)... 

These local anesthetics, including lidocaine (Xylocaine), mepivacaine (Carbo-caine), Prilocaine (Citanest), and bupivacaine (Marcaine) are weak sensitizers, but allergic reactions are sporadically reported, e. g., lidocaine (Turner 1977). Recently Fregert et al. (1979) described two patients developing lidocaine allergy after 8 and 1 month use of Xyloproct ointment (lidocaine 5%, hydrocortisone acetate) they also had positive patch tests to related amide anesthetics, both to mepivacaine, one to bupivacaine and prilocaine. A positive reaction to the chemically unrelated cincaine was interpreted as concomitant sensitivity rather than cross-sensitivity. Safe substitutes for benzocaine-sensitive patients include lidocaine, mepivacaine, prilocaine, bupivacaine, and pyrocaine (Fisher 1973 p. 312), all based on an amide structure. Lidocaine-sensitive patients may use tetracaine (pontocaine), a derivative of aminobenzoic acid. 

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