Esters
1. Cocaine
It is used only in topical anesthesia.
It is used directly in superficial anesthesia of ear-nose-throat, ulcer and wound.
It is a local anesthetic that produces vasoconstriction. It produces vasoconstriction due to local inhibition of noradrenaline reuptake.
Other local anesthetics that cause vasoconstriction without adrenaline are bupivacaine and ropivacaine.
May cause hyperpyrexia.
May cause methemoglobinemia.
It produces bradycardia with vagus central stimulation at low doses and tachycardia at high doses.
2. Procaine
It is a local anesthetic with the weakest potency.
It is the shortest lasting local anesthetic agent.
It is the local anesthetic substance that most often causes allergic reactions.
It should not be administered to people taking sulfonamide therapy as it is converted to PABA in the body.
3. Chloroprocaine
It is contraindicated to use in spinal anaesthesia.
It is not used topically.
Epidural and intrathecal administration is not recommended as it may cause permanent neuronal damage.
Its effect starts quickly and lasts for a short time.
4. Benzocaine
It is used only superficially.
It can be applied directly to wounds and ulcers.
May cause methemoglobinemia.
5. Tetkacaine, Oxybuprocaine, Hexylcaine, Piperocaine etc
Those Made of Amide
• They should not be used in patients with liver disorders and with drugs that reduce liver blood flow, such as propranolol.
• This group of drugs bind to al-acid glycoprotein in plasma. Since this protein is low in infants; They are more sensitive to LAs.
1. Lidocaine
It can be applied in all types of local anesthesia.
Its effect starts quickly.
It can be used intravenously (without adrenaline) as an antiarrhythmic.
It is broken down in the liver, the formed monoethylglycine xylidide and glycine xylidide metabolites have a toxic effect on the CNS (the earliest sign is nystagmus).
Its use in subarachnoid block is limited due to transient neurologic symptoms.
It is excreted through the kidneys.
It should not be used in people susceptible to malignant hyperthermia, as it accelerates the release of calcium from the sarcoplasmic reticulum.
2. Prilocaine
Prilocaine is used in infiltration, peripheral nerve blocks, spinal and epidural anesthesia.
Due to its high clearance, it causes the least systemic toxicity of all amide local anesthetics and is therefore more preferred for intravenous regional anaesthesia.
Together with lidocaine is the most appropriate drug for regional intravenous anesthesia.
Toluidine metabolite formed in the body creates methemoglobinemia.
If methemoglobinemia develops, it is treated with iv methylene blue.
It cannot be used in obstetrics, COPD and cyanotic heart diseases.
3. Mepivacaine
It has a clinical profile similar to lidocaine, but has a slightly longer duration of action because it causes less vasodilation.
It is not used in obstetrics as it is toxic to the baby.
4. Bupivacaine
Bupivacaine is the most lipid soluble local anesthetic, which is the structural homologue of mepivacaine.
Its selectivity to sensory nerve fibers is very high. It provides prolonged sensory anesthesia and analgesia.
Typically the depth and duration of motor block is longer, especially when used with continuous infusion at low concentrations.
It is the strongest (longest acting) of those used systemically.
It is the most cardiotoxic local anesthetic.
It is widely used in subarachnoid anesthesia and typically has a duration of action of 2-3 hours.
In contrast to lidocaine and mepivacaine, transient neurological symptoms are very rare.
It is used for infiltration anesthesia, nerve block, spinal, epidural and caudal anesthesia.
5. Etidocaine
It is the most lipophilic of the local anesthetics.
It provides a good motor block, makes very obvious muscle relaxation.
6. Ropivacaine:
Ropivacaine is the structural homologue of bupivacaine and mepivacaine.
Its fat solubility is lower than bupivacaine.
It is clinically equal in strength with bupivacaine in sensory blockade, but motor block starts more slowly and is of shorter duration.
It has a less cardiotoxic profile compared to bupivacaine.
Having a natural vasoconstrictive effect causes a decrease in cardiotoxic profile and prolongation of its duration of action.
It is more selective to sensory nerve fibers than motor nerve fibers (like Bupivacaine).
It is long-acting LA.
It is used in spinal and regional anesthesia.
7. Levobupivacaine
It is the C-enantiomer of racemic bupivacaine.
Clinically similar to bupivacai.
Less cardiotoxic than bupivacaine.
8. Dibucaine
It is the strongest of local anesthetics in terms of gravimetric potency.
It is one of the most potent and most toxic local anesthetics.
Properties of local anesthetics | |||||
local anesthetic | structure | Usage area | Effect duration | Effect onset | Feature |
Cocaine | Ester | topical | *** | *** | vasoconstriction |
benzocaine | Ester | topical | *** | *** | Topical use only, methemoglobinemia |
procaine | Ester | Topical, infiltration, spinal | Short | Slow | Causes allergies, the shortest and weakest effect |
chlorprocaine | Ester | Infiltration, peripheral nerve block, epidural, spinal (?) | Short | Fast | Spinal use is controversial |
Tetracaine (amethocaine) | Ester | Topical, Spinal | Long | Slow | Very long spinal anesthesia |
dipucaine | amide | Topical, Spinal | Long | Slow | Quite potent and highly toxic |
Etidocaine | amide | Infiltration, peripheral nerve block, epidural | Long | Fast | Most lipophilic LA |
lidocaine | amide | Topical, infiltration, peripheral nerve block, spinal, epidural | Middle | Fast | SSS toxic, antiarrhythmic iv can be used in IVRA |
mepivacaine | amide | infiltration, peripheral nerve block, spinal, epidural | Middle | Slow | Toxic to newborn |
Prilocaine | amide | Infiltration, peripheral nerve block, epidural | Middle | Fast | Methemoglobinemia can be used in IVRA |
bupivacaine | amide | Infiltration, peripheral nerve block, spinal, epidural | Long | Middle | most cardiotoxic |
Ropivacaine | amide | Infiltration, peripheral nerve block, spinal, epidural | Long | Middle | Sensory selective, vasoconstriction |
Levobupivacaine | amide | Major peripheral nerve block, spinal, epidural | Long | Middle | Less cardiotoxic effect |
Side Effects and Toxicity of Local Anesthetics
Systemic Side Effects
• Initially, numbness, dizziness, restlessness, irritability and muscle twitches are seen in the tongue and around the mouth.
• This is followed by convulsions, loss of consciousness.
• Finally, apnea, cardiovascular collapse and coma develop due to medullary depression.
• They can cause intracardiac block and cardiac arrest (especially bupivacaine).
• They may cause hypotension due to sympathetic blockade (especially during spinal and epidural anaesthesia).
• They can cause allergic reactions, mostly seen in ester structures.
• They initially produce a depressant effect in CVS and CNS (except for cocaine, this substance causes euphoria).
• They cause disinhibition-related excitation (tonic-clonic convulsions) at high doses.
• Hypotension (which happens most prominently during spinal anaesthesia)
• Cardiac arrhythmias and cardiac arrest (Bupivacaine)
• Toxic effects on CNS (Lidocaine)
• Increase in body temperature
• Allergic reactions to esters are common (Procaine, Tetracaine).
• P-aminobenzoic acid, which is formed by the breakdown of esters, is responsible for the allergy. (PABA).
Local Anesthetic Systemic Toxicity (LAST) treatment:
• The initial basic treatment required for CNS toxicity is supportive therapy.
• Adequate oxygenation and ventilation should be maintained, and the airway should be secured if necessary.
• Convulsions that persist despite adequate ventilation and oxygenation should be treated with sedative hypnotic agents such as midazolam and propofol. If there is no improvement despite this, a neuromuscular blocker is used to end severe muscle activity.
• In case of cardiac arrest due to LAST, standard advanced cardiac life support should be applied.
• Vasopressin is not recommended and adrenaline is preferred initially.
• If ventricular dysrhythmias develop, amiodarone should be preferred instead of lidocaine.
• Severe CVS toxicity from bupivacaine is resistant to standard resuscitation. In this case, cardiopulmonary bypass should be considered at an early stage for the effective treatment of life-threatening dysrhythmia and cardiovascular collapse.
• It has been shown that intravenous intralipid emulsion significantly reduces bupivacaine-induced CVS toxicity.
