Local anesthetics Lab 4 Dr. Raz Mohammed 27. 3. 2019

Local anesthetics Definition A local anaesthetic can be defined as a drug which reversibly prevents transmission of the nerve impulse in the region to which it is applied, without affecting consciousness.

Structural classification of local anaesthetics Local anaesthetics generally have a lipid-soluble lipophilic aromatic group and a charged, hydrophilic amide group. The bond between these two groups determines the class of the drug, and may be amide or ester.

Types of local anesthetics Ester Procaine………short duration of action Cocaine……….medium duration of action Tetracaine……..long duration of action Benzocaine……topical use only

Amides Lidocaine………medium duration of action Prilocaine………medium duration of action Bupivacaine……long duration of action Etidocaine………long duration of action

Clinically significant differences between esters and amides The ester linkage is more easily broken than the amide bond so the ester drugs are less stable in solution and cannot be stored for as long as amides. Amide anaesthetics are also heat-stable and can therefore be autoclaved; esters cannot. The metabolism of most esters results in the production of para-aminobenzoate (PABA) which is associated with allergic reaction. Amides, in contrast, very rarely cause allergic phenomena. For these reasons amides are now more commonly used than esters.

Mechanism of action of LA Local anaesthetics reversibly block impulse conduction along nerve axons from the periphery to the CNS. This occurs through specific binding of the local anaesthetic molecules to sodium channels by blockade of voltage-gated sodium channels and reduce the influx of sodium ions, so preventing depolarization of the membrane and blocking conduction of the action potential. This effect is mediated from within the cell; therefore the local anaesthetic must be unionized to cross the cell membrane before it can exert its effect.

Clinical use Topical local anesthesia is used for eye, ear, dental, throat, for cosmetic surgery Injection into the epidural or subarachnoid spaces surrounding the spinal cord. L.A requires an agent of rapid penetration of the skin or mucosa and limited tendency to diffuse away from the site of application.

Absorption of LA LA drugs are administered to the areas around the nerves to be blocked – which include skin, subcutaneous tissues, intrathecal and epidural spaces. Some of the drug will be absorbed into the systemic circulation: how much will depend on the vascularity of the area to which the drug has been applied and intrinsic effects of the drug or its additives on vessel diameter.

By adding the vasoconstrictor epinephrine to the local anesthetic, the rate of anesthetic absorption is decreased. This both minimizes systemic toxicity and increases the duration of action.

Why inflammation reduces the action of local anesthetics? This is partly because most of the anesthetic is ionized & therefore unable to cross the cell membrane to reach its cytoplasmic- site of action on the sodium channel. As the pH is reduced the fraction of unionized local anesthetic is reduced and consequently the effect is delayed and reduced. The pH of infected tissue differs from the physiological pH it may be as low as 6.4 in infected tissue. 2. Increase blood flow in inflamed tissues may speed the removal of local anesthesia from injection site. 3. Inflammatory exudates may also inhibit local anesthesia directly by enhancing nerve conduction.