Local anaesthetic additives

Note that the relative spatial arrangement of the phenyl, amine, and hydroxyl functionahties are identical for (R)-alprenolol and (5)-sotalol. In addition to P-blocking activities, some of these compounds also possess potent local anaesthetic activity (see Anesthetics). The membrane stabilizing activity, however, is not stereoselective and correlates directly with the partition coefficient (hydrophobicity) of the compound. 

Whilst tropyltropine (atropine) is mydriatic, this property is of a low order in benz yltropine and is absent in benzoyl- -tropine. The former is a weak and the latter a potent local anaesthetic. This parallelism in the influence of the tropyl and benzoyl radicals in developing mydriatic and local aniesthetic action respectively, has been shown by von Braun and his co-workers to occur through an extensive series of hydroxyalkylamines in addition to tropine. Considerable modification may be made in the structure of tropine without impairing its capacity for yielding mydriatics anaesthetics. Thus von Braun, Muller and Rath found that e tropyl- and benzoyl-esters respectively of liomotropine (I) and of N-hydroxyalkylnortropanes (III) are comparable with atropine and tropacocaine (derived from tropine (II) and 4-tropine (II) ), respectively... 

The preparation and anaesthetic properties of some (N,N-Dialkyl-amino)-alkyl-3-thienylsulfide hydrochlorides were studied 36). As local anaesthetics they were found, in preliminary examinations, to be equal to or better than procaine in activity in the guinea pig test. In addition it was found that the alkaminoesters of phenyl-3-thienylglycolic... 

Catecholamines, when given in combination with local anaesthetics, can induce gangrene in fingers, toes, penis, nose and ears. Local anaesthesia at these locations should be done without an vasoconstrictive additive. 

Noradrenaline and adrenaline are the classic catecholamines and neurotransmitters in the sympathetic nervous system. Noradrenaline stimulates the following subtypes of adrenoceptors P, a, U2. It has positive inotropic and chronotropic activities as a result of /3i-receptor stimulation. In addition, it is a potent vasoconstrictor agent as a result of the stimulation of both subtypes (ai,a2) of a-adrenoceptors. After intravenous infusion, its effects develop within a few minutes, and these actions disappear within 1-2 minutes after stopping the infusion. It may be used in conditions of acute hypotension and shock, especially in patients with very low vascular resistance. It is also frequently used as a vasoconstrictor, added to local anaesthetics. Adrenaline stimulates the following subtypes of adrenoceptors /3i, P2, oil, 0L2. Its pharmacological profile greatly resembles that of noradrenaline (see above), as well as its potential applications in shock and hypotension. Like noradrenaline, its onset and duration of action are very short, as a result of rapid inactivation in vivo. Both noradrenaline and adrenaline may be used for cardiac stimulation. Their vasoconstrictor activity should be kept in mind. A problem associated with the use of /3-adrenoceptor stimulants is the tachyphylaxis of their effects, explained by the /3-adrenoceptor downregulation, which is characteristic for heart failure. 

Pitkanen M, Rosenberg PH. Local anaesthetics and additives for spinal anaesthesia—characteristics and factors influencing the spread and duration of the block. Best Pract Res Clin Anaesthesiol. 2003 17 ... 

Medicinally, cocaine is of value as a local anaesthetic for topical application. It is rapidly absorbed by mucous membranes and paralyses peripheral ends of sensory nerves. This is achieved by blocking ion channels in neural membranes. It was widely used in dentistry, but has been replaced by safer drugs, though it still has applications in ophthalmic and ear, nose, and throat surgery. As a constituent of Brompton s cocktail (cocaine and heroin in sweetened alcohol) it is available to control pain in terminal cancer patients. It increases the overall analgesic effect, and its additional CNS stimulant properties counteract the sedation normally associated with heroin (see page 332). 

Lidocaine] (aryl tertiary amine) Synthetic GABAA-R chloride channel blocker (10,000) [additive with Cocaine, local anaesthetic]... 

ADENOSINE ANAESTHETICS - LOCAL t myocardial depression Additive effect local anaesthetics and adenosine are myocardial depressants Monitor PR, BP and ECG closely... 

Additives to local anaesthetic solutions used include the following ... 

LIDOCAINE PROCAINAMIDE Case report of neurotoxicity when intravenous lidocaine administered with procainamide. No significant interaction expected when lidocaine is used for local anaesthetic infiltration Likely to be an additive effect both may cause neurotoxicity in overdose Care should be taken when administering lidocaine as an infusion for patients taking procainamide... 

LIDOCAINE BETA-BLOCKERS 1. Risk of bradycardia (occasionally severe), l BP and heart failure with intravenous lidocaine 2. Risk of lidocaine toxicity due to T plasma concentrations of lidocaine, particularly with propranolol and nadolol 3. t plasma concentrations of propranolol and possibly some other beta-blockers 1. Additive negative inotropic and chronotropic effects 2. Uncertain, but possibly a combination of beta-blocker-induced 1 hepatic blood flow (due to 1 cardiac output) and inhibition of metabolism of lidocaine 3. Attributed to inhibition of metabolism by lidocaine 1. Monitor PR, BP and ECG closely watch for development of heart failure when intravenous lidocaine is administered to patients on beta-blockers 2. Watch for lidocaine toxicity 3. Be aware. Regional anaesthetics should be used cautiously in patients with bradycardia. Beta-blockers could cause dangerous hypertension due to stimulation of alpha-receptors if adrenaline is used with local anaesthetic... 

Relief of pain after surgery can be achieved with a variety of techniques. An epidural infusion of a mixture of local anaesthetic and opioid provides excellent pain relief after major surgery such as laparotomy. Parenteral morphine, given intermittently by a nurse or by a patient-controlled system, will also relieve moderate or severe pain but has the attendant risk of nausea, vomiting, sedation and respiratory depression. The addition of regular paracetamol and a NSAID, given orally or rectally, will provide additional pain relief and reduce the requirement for morphine. NSAIDs are contraindicated if there is a history of gastrointestinal ulceration of if renal blood flow is compromised. 

The effect of a local anaesthetic is terminated by its removal from the site of application. Anything that delays its absorption into the circulation will prolong its local action and can reduce its systemic toxicity where large doses are used. Most local anaesthetics, with the exception of cocaine, cause vascular dilation. The addition of a vasoconstrictor such as adrenaline (epinephrine) reduces local blood flow, slows the rate of absorption of the local anaesthetic, and prolongs its effect the duration of action of lidocaine is doubled from one to two hours. Normally, the final concentration of adrenaline (epinephrine) should be 1 in 200 000, although dentists use up to 1 in 80 000. 

Adverse effects. In addition to those given above, benzodiazepines can affect memory and balance. Hazards with car driving or operating any machinery can arise from amnesia and impaired psychomotor function, in addition to sleepiness (warn the patient). Amnesia for events subsequent to administration occurs with i.v. high doses, for endoscopy, dental surgery (with local anaesthetic), cardioversion, and in these situations it can be regarded as a blessing. ... 

Constant I, Gall O, Gouyet L, Chauvin M, Murat I. Addition of clonidine or fentanyl to local anaesthetics prolongs the duration of surgical analgesia after single shot caudal block in children. Br J Anaesth 1998 80(3) 294-8. 

The addition of electrolyte or dmgs to intravenous fat emulsions is generally contraindicated because of the risk of destabilising the emulsion. Addition of cationic local anaesthetics reduces the electrophoretic mobility of the dispersed fat globules, and this contributes to instability. Minimum stability (and minimum zeta potential) is caused by addition to Intralipid of 3 x 10 mol dm CaCl2 and 2.5 X 10 mol dm NaCl, which are thus... 

Hexopar inositol nicotinate nicotinic acid, hexoprenaline [ban, inn] (hexoprenaline hydrochloride [jan]) is a P-ADRENOCEPTOR agonist selective for the P2-subtype that therapeutically can be used as a BRONCHODIIATOR in ANTIASTHMATIC treatment, hexoprenaline hydrochloride hexoprenaline. hexuronic acid ascorbic acid, hexylcaine [inn] (hexylcaine hydrochloride [usan]) is an ester series LOCAL ANAESTHETIC, used by topical application for the local relief of pain, hexylcaine hydrochloride hexylcaine. hexylresorcinol [usan] is a urinary ANTISEPTIC and an ANTHELMINTIC. It inhibits melanosis (blackspot) in shrimps, and is used as a food additive for prevention of enzymic browning in shrimps and fruits, hexyltheobromine pentifylline. 

In addition to their action as local anaesthetics, the following actions on other parts of the body are possible. These effects are not clinically significant except in intolerant individuals, those with idiosyncratic reactions, in cases where absorption into the blood stream is unexpectedly rapid or in those with impaired metabolism and/or excretion. 

These vinylogues have the advantage of being more stable towards in vivo metabolism. In addition they allow molecular variations with ortho, meta and para positional isomers. Thus, for cyclovinylogues of procainamide, the highest local anaesthetic activity was found with the meta derivative, which also showed the best dissociation... 

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