Mkgrady8 Neuro 5 Local Anesthestics

they block nerve conduction of both sensory and motor nerves; reversible; block voltage dependent Na channels and thus inhibit action potential generation; noncompetitive antagonist; PORE BLOCKERS; can't enter the pore unless the channel is open THEREFORE A NERVE THAT IS FIRING MORE FREQUENTLY WILL BE MORE SUSCEPTIBLE TO LOCAL ANESTHETIC BLOCK; STABILIZE THE INACTIVATED STATE; locals are voltage dependent because voltage is the regulator of the channel in the first place so depolarizing conditions enhance the probability of opening and hyperpolarizing conditions decrease the probability of opening

most are WEAK BASES with pka's of 8-9; poorly water soluble as the free base so they are typically marketed as a salt in a slightly acid pH (ex. tetracaine HCl); in the body they primarily exist as the ionized cationic form and this can be calculated

pKa-pH=log P/NP; 9-7=2; 2=log of 100/1; so the protonated form exists at a 100x fold excess at pH 7

lipophilicity and conversion of the charged to the uncharged form; the local anesthetic must cross the membrane and then enter the channel pore from the cystosolic side; the binding site for the local anesthetic is near the cytoplasmic end of the channel; small size and lipophilicity are characteristics that make the local anesthetic bind to the Na channel more rapidly; LIPOPHILICITY (and being in the uncharged form) ALLOWS LA TO CROSS MEMBRANE, CHARGED FORM BINDS TO (and blocks) SODIUM CHANNEL

they can block any nerve; the susceptibilty of block is generally viewed as how fast it occurs in a given nerve type; diameter, length, and frequency of firing all contribute to the rate at which block occurs; type C fibers are inhibited more quickly than type B which are inhibited more quickly than type A; in general pain is blocked first then sensory functions, motor is the last to disappear; recovery occurs in the reverse order; the location of a nerve in a bundle can affect its sensitivity for instance if a motor nerve is located a the periphery of a bundle it may be deadened before a sensory nerve that is located more centrally in the bundle

a lipophilic group, an intermediate chain, and a hydrophilic group that is ionizable; there must be come hydrophilicity for the drug to be water soluble and to be capable of diffusing into its site of action; the intermediate chain usually contains an amide or esther linkage to the lipophilic moiety; ester linkages are more susceptible to hydrolysis than are amide linkages

the intrinsic properties of the drug itself; the site of administration; the intrinsic degree of vasodilator activity; drug tissue binding; amides are rapidly taken up and distributed; esters are so prone to immediate hydrolysis that their absorption is of little consequence; lipophilicity related sequestration into fat; the site of injection has to do with vascularity and fat content; the more vasodilatory activity that the drug has the more it is likely to be absorbed; vasocontrictors reduce the absorption

by eliminating blood flow to and from the injection site they can increase the duration of intermediate acting drugs by 50%; they also reduce any toxicity of the local anesthetic because they reduce blood levels; the local anesthetics are all vasodilators to varying degrees except cocaine which is a vasoconstrictor because of sympathomimetic activity; most commonly epi is co administered with the local; other vasoconstrictors that are used are norepi, phenylephrine, and vasopressin; too much vasoconstrictor can lead to local hypoxia so care must be taken; AVOID USE OF VASOCONTRICTORS AT EXTREMITIES= FINGERS, TOES, PENIS, ETC

rapidly metabolizes ester linked local anesthetics; amide linked local anesthetics are metabolized by the hepatic microsomal system so impaired liver function predisposes an individual to toxicity

procaine, chloroprocaine, tetracaine, benzocaine

1st synthetic local anesthetic; it is of low potency, exhibits slow onset, and has a very short duration of action; it, as well as other esters, can produce hypersensitivity reactions in some individuals

a chlorinated analog of procaine and has an even shorter t1/2; these 2 are made for injection and may be used for infiltration or nerve block or spinal anesthesia; both procaine and chloroprocaine are inefficiently absorbed through mucous membranes

has a longer duration; it is available in both topical and injectable forms; because of its slow metabolism it can cause toxicity but slow metabolism results in reduced risk of hypersensitivity compared to procaine; it is frequently used in spinal anesthesia

used less because it its abuse liability and it potential for producing toxicity; it was used at one time as an ophthalmic anesthetic but it produces mydriasis (excessive dilation of pupil) and corneal sloughing; currently it is only used as a respiratory tract anesthetic in a topical form; it can produce severe CNS side effects at high dosage which include tonic clonic seizures and pyrexia; CV side effects are due to local anesthetic action on the heart and sympathetic stimulation; anesthetic actions range from arrhythmias to cardiac failure; sympathetic activity is due to the blockade of catecholamine transport

a topically used ester that is available in ointments and creams

lidocaine, bupivacine

widely used amide LA; longer acting than ester compounds and does not produce hypersensitivity; efficiently absorbed from the mucous membranes and can be used in every route except ophthalmic

an amide that has a very long duration of action; useful by injection but is ineffective locally

IMMUNE SYSTEM (release of histomine from mast cells), CV, AND CENTRAL NERVOUS SYSTEM

the allergic reaction only occurs with some of the esters; it is a result of metabolic production of paraaminobenzoic acid

occurs because of excessive concentrations being absorbed; direct inhibitory actions on the heart muscle include decreased conduction velocity and inotropic effect; CV collapse and death may result from cardiac arrest due to arrhythmia or depression of pacemaker activity; cocaine has the added CV toxicity profile because it has sympathomimetic activity

usually due to inadvertent injection of the anesthetic intravascularly; generalized excitation is thought to be due to suppression of inhibitory pathways (GABAARs and GlyRs); restlessness proceeds to convulsions, coma, and cardiorespiratory arrest; TIME AND DOSE, EXCITATION, DEPRESSION, COMA, DEATH

have been associated with overdose of chorprocaine in spinal anesthesia

by aqueous salts in a number of anesthetics, including benzocaine and lidocaine; there are formulations for use on all body surfaces including the eye; benzocaine is particularly good for burns and other conditions of denuded flesh because it isn't absorbed

the injection of the local anesthetic in a region without regard to the cutaneous route of the nerves; this can be used for superficial tissues or intraabdominal organs

an injection of local anesthetic into or about peripheral nerves or nerve plexuses; both sensory and motor nerves are affected

commonly used for laboring women; the local is injected into the epidural space which is bounded by the ligamentum flacum, dura, and spinal periosteum; it can be injected in the sacral hiatus, or in lumbar, thoracic, or cervical regions; the spinal nerve roots are chiefly affected; a large amount is needed because diffusion is required; HOWERE IS AN OPIATE LIKE FENTANY IS ALSO ONBOARD THE AMOUNT OF LA CAN BE REDUCED SUBSTANTIALLY

an injection of the local around the nerve routes within the subarachnoid space in the lumbar region; the entire lower body can be deadened in such a fashion; positioning of the pt and the used of an appropriate specific gravity of the anesthetic produces the deadening of the desired region; autonomic nerves are extremely sensitive to local anesthetics so CV function is usually depressed; hypotension and poor venous return must be treated aggressively to reduce the possibility of brain damage or kidney failure; HEADACHE can also occur because of the presumed leak of CSF from the hole in the dura

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cocaine= vasoconstrictor, sympathomimetic; benzocaine= only useful topically

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C procine; technically tetracaine is also an ester but it is metabolized slower so it is less likely to have this reaction