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PHARMACODYNAMICS

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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