Page 68 - BSAVA Guide to Pain Management in Small Animal Practice

5 | Pharmacological treatment of pain

VetBooks.ir Structure–activity relationship anaesthetic, the smaller the un-ionized fraction
will be at body pH, delaying the onset of action.
Local anaesthetics typically consist of a
Infected and in amed tissue has a lower p and
hydrophilic amine domain and a hydrophobic
domain, separated by an ester or amide linkage. greater perfusion than normal tissue, so the
They are synthetic derivatives of cocaine, the e ect and duration of action of local
rst compound used for its local anaesthetic anaesthetics may be decreased, to the point of
properties. The local anaesthetics currently making them ine ective in the event of local
used are mostly amides, as esters are more in ltration Schol , ; Becker and Reed,
likely to cause allergic reactions. Amide 6; Paganelli and Popescu, 1 .
anaesthetics are considerably more stable than The pH of local anaesthetic solutions is
esters, and they can even be autoclaved. As a generally low; therefore, they may cause an
rule of thumb, local anaesthetics whose name intense burning sensation at the site of injection,
contains an i before the caine su x have an and this could be relevant in conscious,
amide linkage (lidocaine, bupivacaine, sedated, or lightly anaesthetized animals.
ropivacaine ucker and ather, 1979; Aguirre et Alkalinization of local anaesthetic solutions with
al., 1 ; Becker and Reed, 1 . bicarbonate may reduce the burning sensation
Local anaesthetics are chiral compounds, and reduce the onset time of the e ect,
therefore exist as stereoisomers, and the two increasing the un-ionized form, although
enantiomers may present di erent excessive alkalinization will result in
pharmacokinetic and pharmacodynamic precipitation Englesson, 1974; ucker, 1986;
characteristics. Bupivacaine, for example, is the Patel and Sadoughi, 14 .
racemic mixture of two enatiomers (R(+) and
S , one of which S is marketed as Perineural administration
levobupivacaine) and presents less Sodium channel blockade reduces the
cardiotoxicity. Similarly, ropivacaine is an excitability of the cell membrane, thus a ecting
S-enantiomer (Aguirre et al., 1 ; Becker and the ability of the cell to depolari e. hen a
Reed, 1 ; Patel and Sadoughi, 14 . critical number of sodium channels are blocked
hile ester anaesthetics are metaboli ed in a nerve bre, propagation of electrical signals
by pseudocholinesterase, amide anaesthetics stops. or myelinated bres, a minimum of three
require extensive liver metabolism. The rate of Ranviers’ nodes have to be blocked to stop
removal from the site of injection is crucial for propagation of electrical signals; however,
delivering the drug to the systemic circulation incomplete blockade of more nodes may still
and the site of metabolism and toxicity ; be e ective, provided that the concentration of
therefore, addition of a vasoconstrictor in the the anaesthetic used is not too low, in which
formulation increases the duration of action and case the block becomes inconsistent.
reduces systemic toxicity Braid and Scott, 1966; he larger the nerve bre, the more
Miranda et al., 16 . Similarly, the total dose of anaesthetic is needed to block conduction, and
anaesthetic administered a ects the duration of blockade of unmyelinated bres re uires more
action and the risk of toxicity. anaesthetic compared with myelinated bres of
Local anaesthetics block nerve conduction the same diameter. Clinically, blockade caused
by reversibly binding to the voltage-gated by local anaesthetics shows a di erential onset
sodium channels in the nerve, with greater according to bre diameter and type, rst
a nity for the channel in the active state. he a ecting nociception, then thermal sensation,
site of action is intracellular, and the ionized and nally motor function. his is because
water-soluble formulation is converted to the nociception is transmitted by C bres
un-ionized lipid soluble formulation which is (unmyelinated, but very small) and Aδ bres
able to cross cell membranes, because of the (myelinated, and of small diameter), while motor
di erence between the anaesthetic p and the bres are myelinated and considerably larger.
pH of tissues. The greater the pK of the local Recovery of function follows the reverse order,

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