Nervous system drugs local anesthetics

Although this drug is categorized as a local anesthetic, I have chosen to put it in with the hallucinogens because of the psychotomimetic effects that it produces. Cocaine is not a phenylethyl-amine, but it produces central nervous system arousal or stimulant effects which closely resemble those of the amphetamines, the methylenedioxyamphetamines in particular. This is due to the inhibition by cocaine of re-uptake of the norepinephrine released by the adrenergic nerve terminals, leading to an enhanced adrenergic stimulation of norepinephrine receptors. The increased... 

The cardiovascular effects of local anesthetics result in part from direct effects of these drugs on the cardiac and smooth muscle membranes and from indirect effects on the autonomic nervous system. As described in Chapter 14, local anesthetics block cardiac sodium channels and thus depress abnormal cardiac pacemaker activity, excitability, and conduction. At extremely high concentrations, local anesthetics can also block calcium channels. With the notable exception of cocaine, local anesthetics also depress myocardial contractility and produce direct arteriolar dilation, leading to systemic hypotension. Cardiovascular collapse is rare, but has been reported after large doses of bupivacaine and ropivacaine have been inadvertently administered into the intravascular space. 

Katzung PHARMACOLOGY, 9e > Section V. Drugs That Act in the Central Nervous System > Chapter 26. Local Anesthetics >... 

The development of local anesthetics and their structure-activity relationship are described in Chapter 13 in the drug screening section. Suffice it to say that the development of these drugs has opened up an entirely new era in relieving pain in the conscious patient. When applied locally to nerve tissue in appropriate concentrations, local anesthetics reversibly block the action potentials responsible for nerve conduction. They act on any part of the nervous system and on every type of nerve fiber. Their action is reversible at clinically relevant concentrations and nerve function recovers... 

Interpleural administration of local anesthetics has been followed by Horner s syndrome and increased skin temperature, apparently pointing to an effect on the sympathetic nervous system (162). Pneumothorax or infection can also result. Interpleural administration of local anesthetics can produce high serum drug concentrations and a risk of systemic toxicity (SEDA-21, 13), possibly increased by the addition of adrenaline (SEDA-20,126). 

Only one of these therapeutic uses has turned out to be valid, and that is the use of cocaine as a local anesthetic. When cocaine makes direct contact with peripheral neurons, it prevents neural firing, which has the effect of numbing the area. This action is unlike cocaine s effects on the central nervous system. Cocaine was the first local anesthetic and revolutionized surgery. Now, of course, related -caine drugs such as procaine and xylocaine are used more frequently, but because cocaine also constricts blood vessels, it is still used for surgery on areas such as the face, due to the fact that it reduces bleeding as well as pain. 

Although given locally, the drug may exert a systemic effect because of transport in the blood from the site of administration to other areas, sueh us the heart and central nervous system (CNS). These systemic effect.s. which depend on the concentration of the local anesthetic in the blood, are usually sedation and lighthcudedness. but restlessness, nausea, and anxiety may also occur. High plasma concentrations cun result in convulsions, chiropidy. and coma with rc.spiratory and cardiac depression. 

Nervous system A 22-year-old woman developed paresthesia, a metallic taste, and hot flushes within 20 minutes of administration of intravenous spiramycin for toxoplasmosis during labor [80" ]. The adverse reactions were initially attributed to local anesthetic toxicity associated with epidural analgesia however, epidural catheter aspiration was negative, suggesting that the catheter was not placed intravenously and the temporal relation to spiramycin administration suggested that the drug was the more probable cause. 

Hydrolysis of ester linkages has been found to occur in all animals and bacteria however, the relative rates of hydrolysis in various species can be significantly different. In the case of local anesthetics, their metabohc disposition is of great practical importance since their toxicity depends largely on the balance between their rate of absorption and their rate of destruction. In most animals the esterases which hydrolyze many local anesthetics occur both in the liver and in the plasma. In the case ot human plasma, esterase activity is high and is principally responsible for the inactivation of procaine [60]. Cocaine is principally destroyed by liver esterase in the human, whereas plasma esterase in the rabbit is responsible for the hydrolysis of cocaine. The horse has little effective esterase activity against procaine in either plasma or liver and manifests central nervous system stimulation because of the slow destruction of the drug [61]. 

It is expected that intensive research will be carried out to explore original and unexpected toxicity antidote applications of fat nanoemulsions traditionally used as components of parenteral nutrition therapy. Recently, these authors reviewed the potential role of fat nanoemulsions in treatment of toxicity due to local anesthetics and other lipid-soluble drugs. Litz and coworkers [2008] reported in a 91-yr-patient the reversal of central nervous system and cardiac toxicity after local... 

When systemic or topical pharmacotherapy and other non-invasive approaches provide inadequate relief in patients with NP, interventional approaches may be used, including sympathetic blockade with local anesthetics, intraspinal drug delivery, spinal cord stimulation, peripheral subcutaneous nerve stimulation, or stimulation of specific central nervous system structures, and various neuroablative procedures (e.g. dorsal rhizotomy, neurolytic nerve block, intracranial lesioning). Neuroablative procedures are not reversible and should be reserved for carefully and properly selected patients with intractable pain. 

---