Local anesthetics administration

Malignant hyperthermia Amide local anesthetic administration has been associated with acute onset of fulminant hypermetabolism of skeletal muscle known as malignant hyperthermic crisis. Recognition of early unexplained signs of tachycardia. 

Musculoskeletal In an up-to-date review of the available basic science English literature, the authors describe a consistent finding that local anesthetics have toxic effects on articular chondrocytes and conclude that intra-articular local anesthetics should be used with caution [16 ]. However, the authors point out that comparing the results of multiple models (ex vivo and in vitro), different cell lines from different species and heterogeneous treatment protocols is fraught with difficulties. They suggest that the ideal in vitro or in vivo model is yet to be found to assess the chondrotoxic effects of intra-articular local anesthetic administration. 

Sate the uses of local anesthesia, methods of administration, and nursing responsibilities when administering a local anesthetic. 

Yamamoto F, Hamburger RN Administration of 27 local anesthetics to patients with a history of prior adverse reaction. J Allergy Clin Immunol 1978 61 339-345. 28... 

Epidural anesthesia is administered by injecting local anesthetic into the epidural space. Located outside the spinal cord on its dorsal surface, the epidural space contains fat and is highly vascular. Therefore, this form of anesthesia can be performed safely at any level of the spinal cord. Furthermore, a catheter may be placed into the epidural space, allowing for continuous infusions or repeated bolus administrations of anesthetic. 

Prilocaine (4.138), a chiral local anesthetic, was hydrolyzed stereoselec-tively at its amide bond. Indeed, the plasma concentrations of the (-)-(/ )-enantiomer were lower than those of the (+)-(5 )-enantiomer after i.v. administration in the cat. In vitro studies of liver preparations from various mammals confirmed that the (R)-isomer was hydrolyzed at much higher rates than the (.S )-form [84],... 

Clove is listed as Generally Regarded as Safe (GRAS) by the U.S. Food and Drug Administration, and is approved by the German Commission E for use as a local anesthetic. 

Amide-type agents include articaine, lidocaine, bupivacaine, prilocaine, mepivacain and ropiva-caine. These are metabolized in the liver by microsomal enzymes with amidase activity. The amide group is preferred for parenteral and local use. If by accident rapidly administered intravascularly these agents, especially bupivacaine but also lidocaine, can produce serious and potentially lethal adverse effects including convulsions and cardiac arrest. They can more easily accumulate after multiple administrations. Intravenous lidocaine is sometimes used for regional anesthesia, for infiltration procedures, for the induction of nerve blockade and for epidural anesthesia. However, it is also used as an antiarrhythmic. Bupivacaine is a long-acting local anesthetic used for peripheral nerve blocks and epidural anesthesia. 

Ziconotide is a non-opioid, non-NSAID, non-local anesthetic used for the amelioration of chronic pain. In December 2004 the FDA approved ziconotide for intrathecal administration. The drug is derived from a marine snail toxin. Its mechanism of action has not yet been elucidated. Due to serious side effects or lack of efficacy when delivered through more conventional routes ziconotide must be administered in-trathecally. It s use is considered appropriate only for management of severe chronic pain in patients for whom intrathecal therapy is indicated. 

The vasoconstrictor actions of epinephrine and norepinephrine have been used to prolong the action of local anesthetics by reducing local blood flow in the region of the injection. Epinephrine has been used as a topical hemostatic agent for the control of local hemorrhage. Norepinephrine is infused intravenously to combat systemic hypotension during spinal anesthesia or other hypotensive conditions in which peripheral resistance is low, but it is not used to combat the hypotension due to most types of shock. In shock, marked sympathetic activity is already present, and perfusion of organs, such as the kidneys, may be jeopardized by norepinephrine administration. 

Quinidine administration results in a dose-dependent depression of membrane responsiveness in atrial muscle fibers. The maximum rate of phase 0 depolarization and the amplitude of phase 0 are depressed equally at all membrane potentials. Quinidine also decreases atrial muscle excitability in such a way that a larger current stimulus is needed for initiation of an active response. These actions of quinidine often are referred to as its local anesthetic properties. 

Because of its anticholinergic properties, disopyramide should not be used in patients with glaucoma. Urinary retention and benign prostatic hypertrophy are also relative contraindications to disopyramide therapy. Patients with myasthenia gravis may have a myasthenic crisis after disopyramide administration as a result of the drug s local anesthetic action at the neuromuscular junction. The elderly patient may exhibit increased sensitivity to the anticholinergic actions of disopyramide. 

The most commonly used vasoconstrictors, the sympathomimetic drugs, are often added to local anesthetics to delay absorption of the anesthetic from its injection site. By slowing absorption, these drugs reduce the anesthetic s systemic toxicity and keep it in contact with nerve fibers longer, thereby increasing the drug s duration of action. Administration of lidocaine 1% with epinephrine results in the same degree of blockade as that produced by lidocaine 2% without the vasoconstrictor. 

Mechanism of Action An amide-type local anesthetic that shortens the action potential duration and decreases the effective refractory period and automaticity in the His-Purkinje system of the myocardium by blocking sodium transport across myocardial cell membranes. Therapeutic Effect Suppresses ventricular arrhythmias. Pharmacokinetics Very rapidly and completely absorbed following PO administration, Protein binding 10%, Metabolized in liver. Excreted in urine. Half-life 15 hr. 

Which of the following local anesthetics is useful for topical (surface) administration only ... 

Local anesthetics are frequently coadministered with vasoconstrictor molecules such as epinephrine. Normally, they are applied or injected locally and then taken up by local blood vessels into the systemic circulation, ultimately leading to their metabolic breakdown. The co-administration of a vasoconstrictor decreases the systemic absorption of the local anesthetic, thereby increasing its effective half-life in the area of administration and decreasing the probability of systemic toxicity (i.e., cardiac toxicity) secondary to systemic distribution. 

Reduction of local or regional blood flow is desirable for achieving hemostasis in surgery, for reducing diffusion of local anesthetics away from the site of administration, and for reducing mucous membrane congestion. In each instance, -receptor activation is desired, and the choice of agent depends on the maximal efficacy required, the desired duration of action, and the route of administration. 

Combining agonists with some local anesthetics greatly prolongs the duration of infiltration nerve block the total dose of local anesthetic (and the probability of toxicity) can therefore be reduced. Epinephrine, 1 200,000, is the favored agent for this application, but norepinephrine, phenylephrine, and other agonists have also been used. Systemic effects on the heart and peripheral vasculature may occur even with local drug administration but are usually minimal. 

Local anesthetic action, also known as "membrane-stabilizing" action, is a prominent effect of several 3 blockers (Table 10-2). This action is the result of typical local anesthetic blockade of sodium channels (see Chapter 26) and can be demonstrated experimentally in isolated neurons, heart muscle, and skeletal muscle membrane. However, it is unlikely that this effect is important after systemic administration of these drugs, since the concentration in plasma usually achieved by these routes is too low for the anesthetic effects to be evident. These membrane-stabilizing 3 blockers are not used topically on the eye, where local anesthesia of the cornea would be highly undesirable. Sotalol is a nonselective 3-receptor antagonist that lacks local anesthetic action but has marked class III antiarrhythmic effects, reflecting potassium channel blockade (see Chapter 14). 

Recovery is sufficiently rapid with most intravenous drugs to permit their use for short ambulatory (outpatient) surgical procedures. In the case of propofol, recovery times are similar to those seen with sevoflurane and desflurane. Although most intravenous anesthetics lack antinociceptive (analgesic) properties, their potency is adequate for short superficial surgical procedures when combined with nitrous oxide or local anesthetics, or both. Adjunctive use of potent opioids (eg, fentanyl, sufentanil or remifentanil see Chapter 31) contributes to improved cardiovascular stability, enhanced sedation, and perioperative analgesia. However, opioid compounds also enhance the ventilatory depressant effects of the intravenous agents and increase postoperative emesis. Benzodiazepines (eg, midazolam, diazepam) have a slower onset and slower recovery than the barbiturates or propofol and are rarely used for induction of anesthesia. However, preanesthetic administration of benzodiazepines (eg, midazolam) can be used to provide anxiolysis, sedation, and amnesia when used as part of an inhalational, intravenous, or balanced anesthetic technique. 

Some pharmacokinetic properties of the commonly used amide local anesthetics are summarized in Table 26-2. The pharmacokinetics of the ester-based local anesthetics have not been extensively studied owing to their rapid breakdown in plasma (elimination half-life < 1 minute). Local anesthetics are usually administered by injection into dermis and soft tissues around nerves. Thus, absorption and distribution are not as important in controlling the onset of effect as in determining the rate of offset of local analgesia and the likelihood of CNS and cardiac toxicity. Topical application of local anesthetics (eg, transmucosal or transdermal) requires drug diffusion for both onset and offset of anesthetic effect. However, intracavitary (eg, intra-articular, intraperitoneal) administration is associated with a more rapid onset and shorter duration of local anesthetic effect. 

Since blood levels are lowered up to 30% when vasoconstrictors are added to local anesthetics, localized neuronal uptake is enhanced because of higher local tissue concentrations in the region of drug administration, and the risks of systemic toxic effects are reduced. Furthermore, when used in spinal anesthesia, epinephrine acts directly on the cord to both enhance and prolong local anesthetic-induced spinal anesthesia by acting on a2 adrenoceptors, which inhibit release of... 

The amide local anesthetics are widely distributed after intravenous bolus administration. There is also evidence that sequestration can occur in lipophilic storage sites (eg, fat). After an initial rapid distribution phase, which consists of uptake into highly perfused organs such as the brain, liver, kidney, and heart, a slower distribution phase occurs with uptake into moderately well-perfused tissues, such as muscle and the gastrointestinal tract. As a result of the extremely short plasma half-lives of the ester type agents, their tissue distribution has not been extensively studied. 

Local anesthetics have poorly understood effects on inflammation at sites of injury, and these anti-inflammatory effects may contribute to improved pain control in some chronic pain syndromes. At the concentrations used in spinal anesthesia, local anesthetics can inhibit transmission via substance P (neurokinin-1), NMDA, and AMPA receptors in the secondary afferent neurons (Figure 26-1). These effects may contribute to the analgesia achieved by subarachnoid administration. Local anesthetics can also be shown to block a variety of other ion channels, including nicotinic acetylcholine channels in the spinal cord. However, there is no convincing evidence that this mechanism is important in the acute clinical effects of these drugs. High concentrations of local anesthetics in the subarachnoid space can interfere with intra-axonal transport and calcium homeostasis, contributing to potential spinal toxicity. 

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