Local Anesthesia Lecture 18 PDF

Lecture -18 - Pharmacology 2024-2025 ‫أزهر عبد الحافظ جابر‬.‫د‬ Local Anesthesia (LA) Local anesthetics (LAs) abolish sensation (and, in higher concentration motor activity) in a limited area of the body without producing unconsciousness. M...

Lecture -18 - Pharmacology 2024-2025 ‫أزهر عبد الحافظ جابر‬.‫د‬ Local Anesthesia (LA) Local anesthetics (LAs) abolish sensation (and, in higher concentration motor activity) in a limited area of the body without producing unconsciousness. Mechanism of action of LAs: The primary mechanism of action of LAs is blockade of voltage-gated sodium channels. They raise threshold of excitability, preventing the initiation and propagation of the nerve impulse (action potential).  Desired properties of local anesthetic (LAic) agents: 1. Water soluble. 2. Sterilizable by heat. 3. Rapid onset of effect. 4. Appropriate duration of action (to the operation to be performed). 5. Non-toxic (both locally and when absorbed into the circulation). 6. Leave no local after-effects. NB: So many compounds have LAic properties, but few are suitable for clinical use. Pharmacokinetics of LAs: Most LAs are used in the form of the acid salts, as these are both soluble and stable. The acid salts (usually hydrochloride salts pH 4.0 – 6.0) are buffered in the tissue to physiologic pH, thereby providing sufficient free base (which is biologically active) for diffusion through axonal membranes. This dissociation is delayed in abnormally acid (e.g., inflamed) tissues; for that 1 Page reason and because of the risk of spreading infection, the use of LA is undesirable in infected areas. Moreover, repeated injections deplete the buffering capacity of the local tissues and the resulting acidosis increases the extracellular cationic form, which diffuses poorly into axons. The clinical result is apparent tachyphylaxis (loss of effectiveness after repeated administration).  Lecture -18 - Pharmacology 2024-2025 ‫أزهر عبد الحافظ جابر‬.‫د‬ ▪ Absorption from mucous membranes on topical application varies according to the compound. Those that are well absorbed are used as surface anaesthetics (cocaine, lidocaine, prilocaine). ▪ Absorption of topically applied LAs can be extremely rapid and give plasma concentrations comparable to those obtained by injection. This has led to deaths from overdose, especially via the urethra. ▪ For topical effect on intact skin for needling procedures a tetracaine gel 4% is effective and allows pain free venepuncture 30 minutes after application. Classification of LAs 1. Ester compounds (cocaine, procaine, tetracaine, benzocaine) are hydrolysed by liver and plasma esterases and their effects may be prolonged where there is genetic enzyme deficiency. 2. Amide compounds [lignocaine (lidocaine), prilocaine, bupivacaine, ropivacaine] are dealkylated in the liver. ▪ Impaired liver function, whether due to primary cellular insufficiency or to low liver blood flow as in cardiac failure, may both delay elimination and allow higher peak plasma concentrations of both types of local anaesthetic. ▪ This is likely to be important only with large or repeated doses or infusions. These considerations are important in the management of cardiac arrhythmias by i.v. infusion of lignocaine (lidocaine). Uses of LAs: 2 Page ▪ Local anaesthesia is generally used when loss of consciousness is neither necessary nor desirable. ▪ Also as an adjunct to general anesthesia in major surgery to avoid high-dose general anaesthesia and to provide postoperative analgesia. ▪ It can be used for major surgery, with sedation, though many patients prefer to be unconscious.  Lecture -18 - Pharmacology 2024-2025 ‫أزهر عبد الحافظ جابر‬.‫د‬ Local anesthetics may be used in several ways to provide: 1. Surface anaesthesia, as solution, jelly, cream or lozenge. 2. Infiltration anaesthesia, to block the sensory nerve endings and small cutaneous nerves 3. Regional anaesthesia: a. Nerve block (injection around a nerve or plexus) b. IV regional anesthesia (using a double cuff) c. Extradural (epidural) d. Subarachnoid (spinal anesthesia).  Nerve block provides its own muscular relaxation as motor fibers are blocked. Sympathetic nerve blocks may be used in vascular disease to induce vasodilatation.  IV regional anesthesia: ▪ Action occurs in 6-8 minutes. ▪ The effect lasts for up to 40 min. if the cuff remains inflated. ▪ The cuff must not be deflated for at least 20 minutes. ▪ Useful for treatment of injuries speedily ▪ Careful technique should be applied, because if the full dose of local anaesthetic is accidentally suddenly released into the general circulation severe toxicity and even cardiac arrest may result. Bupivacaine is no longer used for intravenous regional anaesthesia as cardiac arrest caused by it is resistant to 3 Page treatment. ▪ Patients should be fasted and someone skilled in resuscitation must be present.  Extradural (epidural) anaesthesia: is used in the thoracic, lumbar and sacral (caudal) regions. Lumbar epidurals are used widely in obstetrics The drug is injected into the extradural space where it acts on the nerve roots. (less likely to cause hypotension than spinal anaesthesia).  Lecture -18 - Pharmacology 2024-2025 ‫أزهر عبد الحافظ جابر‬.‫د‬  Subarachnoid (intrathecal) block (spinal anesthesia): Injection of a LAic into CSF. By using a solution of appropriate specific gravity and tilting the patient, the drug can be kept at an appropriate level. Sympathetic nerve blockade causes hypotension. Serious local neurological complications, for example infection and nerve injury, are extremely rare (by expert hands). Opioid analgesics are used intrathecally and extradurally. ▪ They diffuse into the spinal cord and act on its opioid receptors; ▪ they are highly effective in skilled hands for postsurgical and intractable pain. ▪ The effect begins in 20 min and lasts about 5 hrs. Diamorphine or other more lipid-soluble opioids, such as fentanyl, may be used Individual local anesthetics: 1. Amides: ▪ Lignocaine (lidocaine): is a first choice drug for surface use as well as for injection, combining efficacy with comparative lack of toxicity; the t1/2 is 1.5hr. It is also useful in cardiac arrhythmias although it is being replaced by amiodarone for this purpose. ▪ Prilocaine is used similarly to lidocaine (t1/2=1.5h), but it is slightly less toxic. 4 Page ▪ Bupivacaine is long-acting (t1/2 = 3 h) and is used for peripheral nerve blocks, and epidural and spinal anaesthesia. Its onset of effect is comparable to lidocaine, but its peak effect occurs later (30 min). ▪ Ropivacaine may provide better separation of motor and sensory nerve blockade; effective sensory blockade can be achieved without causing motor weakness.  Lecture -18 - Pharmacology 2024-2025 ‫أزهر عبد الحافظ جابر‬.‫د‬ 2. Esters: ▪ Cocaine: is an alkaloid used medicinally solely as a surface anaesthetic usually as a 4% solution, because adverse effects are both common and dangerous when it is injected. ▪ Cocaine prevents the uptake of catecholamines [adrenaline (epinephrine), noradrenaline (norepinephrine)] into sympathetic nerve endings, thus increasing their concentration at receptor sites, so that cocaine has a built-in vasoconstrictor action, which is why it retains a (declining) place as a surface anaesthetic for surgery involving mucous membranes, e.g. nose. Most other local anesthetics are vasodilators and added adrenaline (epinephrine) is not so efficient. ADVERSE REACTIONS: ▪ Excessive absorption results in paresthesia (face and tongue), anxiety, tremors and even convulsions. The latter are very dangerous, are followed by respiratory depression and may require diazepam or thiopental for control. ▪ Cardiovascular collapse and respiratory failure occur with higher plasma concentrations of the local anaesthetic and is caused by direct myocardial depression compounded by hypoxia associated with convulsions. Cardiopulmonary resuscitation must be started immediately. ▪ Anaphylactoid reactions are very rare with amide local anesthetics and some of those reported have been due to preservatives. Most reported reactions to 5 Page amide local anesthetics are due to co-administration of adrenaline (epinephrine), intravascular injection or psychological effects (vasovagal episodes). Reactions with ester local anesthetics are more common. Prolongation of action of LAs: ▪ Most LAs (except cocaine) cause vasodilation ▪ The effect of a LAic terminated by its removal from the site of application. ▪ The addition of a vasoconstrictor such as adrenaline will reduce local blood flow and slow the rate of absorption of a LAic and prolongs its effect and  Lecture -18 - Pharmacology 2024-2025 ‫أزهر عبد الحافظ جابر‬.‫د‬ reduce the systemic toxicity where large doses of a LAic are used. (e.g., the duration of action of lidocaine is doubled from 1 to 2 hrs when adrenaline is added. ▪ The final concentration of adrenaline should be 1 in 200000 (5 microgram/ml), although, dentists use up to 1 in 80000 (12.5 microgram/ml) ▪ The total dose of adrenaline should not exceeds 500 microgram.  Notes: 1. Do not use a vasoconstrictor for nerve block of an extremity (finger, toe, nose, penis) (the whole blood supply may be cut off by intense vasoconstriction causing organ damage or loss) 2. Felypressin (a synthetic vasopressin) is used as an alternative vasoconstrictor to adrenaline. It does not affect the rate of heart or blood pressure, it may be preferable in patients with cardiovascular disease. 6 Page