Local Anesthetic Agents. Prepared By: Rasha AL- Mobark . Haifa AL- Semeri . Alaa Mously . Maged Aggab . Fatimah Hawsawi . Contents: Introduction. Historical development. Action Potential Mechanism of Action. Administration.
Blocking drugs that, when administrated locally “ block” the nerves that carry impulses in local areas of the body and the action is reversible.
Their method of administration is governed by such properties as toxicity, stability, duration of action, water solubility, membrane permeability, and point of application.
Their systemic effects, depends on the concentration of the local anesthetic in the blood.
Koller also recommended the use of cocaine as local anesthetic in ear, nose and throat operation.
In 1904 (Led Braun) determination to design drug based on the stucture of both adrenaline and cocaine . It was marketed as Novocaine then approved under procaine.
the amine group increase the reactivity of the ring
Open the pipriden ring to decrease toxicity
At resting statusthe potential is be -70
In the initial depolarizationthe firing threshold rapid stimulation increase the potential to -40, here starts feeling the pain.
NA+ channels is open and increase positive in intracellular while k+ will increase in extracellular.
Direct application of a local anesthetic agent to the skin or mucous membrane blocks the sensory nerve endings, producing temporary loss of sensation in a limited area.
In the form of : liquid, spray, cream, ointment, or gel.
used to anesthetize a large region , such as a limb . The anesthetic is injected into a suitable vein in a limb that has had its blood flow restricted by a tourniquet .
It is carried out by injecting the anesthetic agent into the subarachnoid space in the spinal cord .
small nonmyelinated fibers > small myelinated fibers > large fibers.In experimental work, the outer fibers in the nerve are affected first , regardless of their
Local anesthetic are normally weak bases
(pka 8.5) which are only slightly soluble in water.They are marketed as aqueous solution of their soluble salt.Although the drug is mainly transferred through the cell membrane in its free base form. Administration of the drug in alkaline solution does not enhance its activity. This is because the structure of the drug is controlled by the pH of the extracellular fluid and not the PH of the dosage form.
Adrenaline1-the agent is confined to the site of action reducing the rate at which the blood carries it away.
2-it is also reduce the rate of absorption of a drug by allowing the metabolic rate of local anesthetic to keep pace with the rate at which it is absorbed into blood stream .
1. Adrenaline ( epinephrine ).2. Noradrenaline ( norepinephrine).3.felypressin.
The effect of vasoconstrictor depends on the local anesthetic agent used;adrenaline significantly prolongs the action lignocaine but has less effect with prilocaine
The concentration of vasoconstrictor are kept as low as possible to reduce the risk of unwanted side effects: such as chest pain , palpitations and increase heart rate.
Consequently, restriction of blood supply can cause necrosis , a form of enforced cell death.
Preparations containing adrenaline should not normally used on patients with diseases including poorly controlled diabetes, cardiovascular diseases and thyrotoxicosis
Cocaine is vasoconstrictor and so probably owes some of its effectiveness to this property .
The effectiveness of the blocking action in a given concentration of a local anesthetic agent depends on the frequency and extent to which the neuron has been recently stimulated.
Ester or amide Group
Short hydrocarbon chain or O, N, or sulfur atoms
2nd or 3rd amine
But 3rd more useful
Either a carbocyclic or heterocyclic ring
Lipid solubility plays an important part in the action of local anesthetics (on their ability to penetrate the cell membrane of axon).
Lipophilic Group—Amide—Bridging Group—Hydrophilic Group(if any)