PHARMACODYNAMICS of LOCAL ANESTHESIA (ANAESTHESIA)

PHARMACODYNAMICS Listen to Audio Effects on organ systems Drug Interaction EFFECTS ON ORGAN SYSTEMS Central nervous system -vulnerable to local anesthetic toxicity -usually one of the first signs of anesthetic toxicity in an awake patient Early symptoms: circumoral numbness, tongue paraesthesia, and dizziness Sensory complaints: tinnitus and blurred vision Excitatory signs: restlessness, agitation, nervousness, paranoia CNS depression: slurred speech, drowsiness, unconsciousness -tonic clonic seizure often follows the beginning of muscle twitching -respiratory arrest generally follows CNS toxicity (seizures) -thiopental 1-2 mg/kg generally used to treat seizures and airway management is immediately required Prolonged neurologic deficit : with large volumes of chloroprocaine unintentionally injected intrathecally instead of epidural Cauda equina syndrome: -repeated doses of lidocaine 5% and tetracaine 0.5% may be responsible for neurotoxicity -infusion of continous spinal anesthesia through a small-bore cathetor -may result from high concentration of local anesthetics pooling around the cauda equina leading to permanent neuronal damage Transient neurologic symptoms: -burning pain, dysesthesia, and aching of the buttocks and lower extremities following spinal anesthesia -possibly from radicular irritation -symptoms generally resolve within 1 week Cardiovascular system local anesthetics generally: -depress the automaticity (phase 4 spontanous depolarization) -decrease the duration of the refractory period -decrease myocardial contractility at higher anesthetic concentrations -decrease myocardial conduction velocity at higher anesthetic concentrations -inhibition of the autonomic nervous system -arterial smooth muscle relaxation -all of the above can lead to decreased arterial pressure, heart block and cardiac arrest Bupivicaine toxicity -unintentional intravascular injection of bupivicaine has been associated with severe cardiotoxic reactions -hypotension -atrioventricular heart blocks -dysrhythmias ex. ventricular fibrillation -high degree of protein binding makes bupivicaine toxicity difficult to treat Respiratory -apnea may result from phrenic and intercostal block and depression of the medullary respiratory centers -local anesthetics relax bronchial smooth muscles ex. lidocaine 1.5 mg/kg may prevent bronchoconstriction sometimes associated with ETT intubation -lidocaine depresses hypoxic drive Hematologic -lidocaine may decrease coagulation -lidocaine may also increase fibrinolysis Immunologic -allergic reactions may occur ex. PABA allergic reactions -may inhibit neutrophil function and may slow wound healing Musculoskeletal -myotoxic when injected into muscle -myofibril hypercontraction may progress to lytic degeneration and finally into edema and necrosis -regeneration may occur upto 3 - 4 weeks DRUG INTERACTIONS -local anesthetics prolongs duration of nondeplarizing muscle relaxants (NDMR) -metabolism of succinylcholine and ester local anesthetics both depend on pseudocholinesterase -dibucaine amide local anesthetic inhibits the enzyme pseudocholinesterase which helps determine genetic enzymatic abnormalities -cimetidine and propanolol decrease hepatic blood flow and also decrease the hepatic clearance of lidocaine -opids generally prolong and assist in local anesthetic function of pain relief.