Local anesthetics are a kind of drugs applied locally around nerve endings or nerve trunks, which can temporarily, completely and reversibly block the generation and conduction of nerve impulses and make local pain disappear temporarily in conscious state. It has no damage to various tissues.
pharmacological action
1. Local anesthesia and its mechanism. Local anesthetics can block any nerve and no longer cause depolarization to any stimulus. Local anesthetics can also inhibit the activity of smooth muscle and skeletal muscle at high concentration.
The anesthesia order of local anesthetics on nerves and muscles is: pain, warm feeling of fiber contact, inhibitory nerve center of fiber center, autonomic nerve movement, nerve myocardium (including conductive fibers), vascular smooth muscle, gastrointestinal smooth muscle, uterine smooth muscle and skeletal muscle.
Local anesthetics act on the inner side of Na+ channel of nerve cell membrane, inhibit the influx of Na+ and prevent the generation and conduction of action potential. Further study found that the local anesthetic combined with the receptor in the Na+ channel, which caused the protein conformation change of the Na+ channel, closed the gate of the inactivation state of the Na+ channel, and blocked the influx of Na+, thus resulting in local anesthesia.
2. Toxic reaction caused by absorption of local anesthetics.
(1) The central nervous system is excited first and then inhibited, and the initial manifestations are dizziness, restlessness and muscle tremor. Then it developed into delirium and generalized tonic clonus. Finally turned into a coma, respiratory paralysis. Inhibitory neurons in the central nervous system are sensitive to local anesthetics, and are first inhibited by local anesthetics, thus causing disinhibition and excitement. The convulsion caused by local anesthetics is caused by the diffusion of excited focus in the limbic system. Benzodiazepines can enhance the inhibitory effect of GABAergic neurons in the limbic system, and have a good effect on toxic convulsions caused by local anesthetics. Central inhibitory drugs are prohibited at this time. During poisoning coma, we should focus on maintaining respiratory and circulatory functions.
(2) Local anesthetics of cardiovascular system can be directly inhibited. At first, blood pressure rises, and the heart rate increases (central excitement), then the heart rate slows down, blood pressure drops, and conduction block stops until the heart stops beating. Breathing usually stops after poisoning, and artificial respiration should be used for rescue.
Local anesthesia method
Surface anesthesia: also known as mucosal anesthesia. Used on mucosal surface to anesthetize the sensory nerve endings under the mucosa by drug infiltration. Commonly used in otolaryngology surgery.
Infiltration anesthesia: drugs are injected into intradermal, subcutaneous, submucosal or deep tissues of the surgical site to infiltrate sensory nerve endings, resulting in local anesthesia. Used for superficial minor surgery.
Conductive anesthesia: also known as block anesthesia. It is to inject liquid medicine around the nerve trunk to block the conduction of the nerve trunk and make the area dominated by the nerve trunk produce anesthesia. Commonly used in limb, pelvic cavity, perineum and dental surgery.
Spinal anesthesia: also known as spinal block anesthesia, referred to as spinal anesthesia. Liquid medicine is injected into the subarachnoid space of spinal cord to block the conduction of spinal nerve roots, resulting in extensive anesthesia. Suitable for middle and lower abdomen and lower limbs surgery.
Epidural anesthesia: the liquid medicine is injected into the epidural space and diffused to the intervertebral foramen along the spinal nerve root to anesthetize the spinal nerve root. Suitable for upper and lower abdomen and lower limb surgery. However, due to the large dose, it is necessary to prevent accidental entry into subarachnoid space.
[Adverse reactions] Except for different varieties, poor tolerance, allergies, etc. They are all related to dose; Often due to excessive, rapid absorption or accidental injection into the blood circulation, the blood drug concentration is high.
1. Rare adverse reactions include: ① methemoglobinemia, occasionally seen in a few local anesthetics such as bupivacaine; ② Blurred vision or diplopia, convulsion or convulsion, chills or tremors, dizziness and tinnitus, abnormal excitement, irritability and even coma, abnormal vomiting, hyperhidrosis, hypotension and bradycardia are mostly precursors of poisoning caused by high blood drug concentration; ③ Rash or measles, swelling and pain of face, lips or throat are allergic reactions; Esters are much more than amides.
2. The general adverse reactions during injection may include headache or backache, incontinence, loss of libido, numbness of limbs (especially lower limbs), shortness of breath or difficulty, hypotension and bradycardia.
3. During local anesthesia in dentistry, the lips may have numbness, tremor or edema for a long time.
4. Adrenaline is added to the local anesthetic solution, which may cause dizziness or headache, chest pain and elevated blood pressure.
[Drug Interaction]
1. All local anesthetic solutions are acidic and must not be mixed with alkaline solutions; Even if both of them are acidic, they can affect the pKa value of each local anesthetic, weakening the effect of local anesthetic or delaying the onset time.
2. Esters with p-aminobenzoic acid structure are combined with sulfonamides, which reduces the interaction between them.
3. dyclonine and radioactive imaging drugs containing iodine will precipitate iodine.
4. Both procaine and lidocaine can enhance the muscle relaxation of succinylcholine, and the dosage of the latter should be reduced when combined.
5. Intravenous procaine has been tried as an auxiliary drug for general anesthesia. However, it can promote the synergistic effect of inhalation and intravenous general anesthesia, and the dosage should be reduced when combined.
Factors affecting the action of local anesthetics
1. Nerve trunk or thick nerve trunk of nerve fiber is wrapped by sheath, and the effect of local anesthesia on it is not as good as that on nerve endings, so the concentration required for conduction anesthesia is higher, about 2 ~ 3 times that of infiltration anesthesia. Coarse nerve fibers (such as motor nerves) are less sensitive to local anesthetics than fine nerve fibers (such as pain nerves and sympathetic nerves).
2. Body fluid pH local anesthetics can be divided into nonionic and ionic types in vivo. Non-ionic lipophilic, easy to penetrate cell membrane and enter nerve cells to play a local anesthetic role. When the pH value of body fluid is high, there are more nonionic types, and the local anesthesia effect is enhanced. On the contrary, local anesthesia is weakened. The pH value in the inflamed area decreases, so the effect of local anesthetics is weakened. Before abscess incision, annular infiltration must be carried out around the abscess to be effective.
3. Drug concentration: increasing the concentration can not prolong the maintenance time of local anesthesia, but accelerate absorption and cause poisoning. Drugs with the same concentration should be injected in batches.
4. Adding a small amount of adrenaline into vasoconstrictor can make local blood vessels contract, slow down drug absorption, prolong local anesthesia maintenance time and reduce absorption poisoning. Adrenaline is prohibited in peripheral parts such as fingers, toes and penis (causing local tissue necrosis).
【 Common local anesthetics 】
1. procaine is the most commonly used, has low lipophilicity, is not easy to penetrate mucosa, and is only used for injection. Widely used in infiltration anesthesia, conduction anesthesia, subarachnoid anesthesia, epidural anesthesia and local sealing of injured parts. Its metabolite p-aminobenzoic acid (PABA) can resist the antibacterial effect of sulfonamides. Occasionally allergic reaction, skin allergy test should be done before medication. Allergies can be replaced by lidocaine.
2. Lidocaine is faster, stronger, more durable and has a wider range of safety than procaine. Lidocaine can penetrate mucosa and can be used in various local anesthesia methods. Mainly used for conduction anesthesia and epidural anesthesia. It can also be used for antiarrhythmia.
3. Tetracaine, also known as tetracaine, is stronger than procaine 10 times in function and toxicity, with high lipophilicity and strong penetration, which is easy to enter the nerve and be absorbed into the blood. It is most commonly used for surface anesthesia, spinal anesthesia and epidural anesthesia, and is generally not used for infiltration anesthesia. The hydrolysis rate of cholinesterase in blood is slower than that of procaine, so the action time is longer, about 2 ~ 3 hours.
4. Bupivacaine, also known as bupivacaine, has the longest duration of action among commonly used local anesthetics, about 5 ~ 10 hour. Its local anesthetic effect is 4 ~ 5 times stronger than lidocaine, its safety range is wider than lidocaine, and it has no vasodilation effect. It is mainly used for infiltration anesthesia, conduction anesthesia and epidural anesthesia.
Introduction to central nervous system pharmacology (pre-exam counseling)
Transmitters and receptors in the central nervous system
More than 30 kinds of central transmitters are known. This paper introduces several important transmitters, receptors and their functions.
1 and acetylcholine (Ach) are widely distributed in the central nervous system. Receptors are divided into M-type and N-type, and their functions are related to exercise, memory, vigilance and visceral activities. Ach in the central nervous system is mainly an excitatory transmitter. For example, when an animal is stimulated, Ach is released in the brain, but it decreases during sleep.
2. The distribution of norepinephrine (NA)NA is concentrated in the central nervous system, mainly in the hypothalamus. Receptors are divided into α-type and β-type, and their functions are related to the regulation of alertness, sleep and mood. When the activity of NA neurons in the central nervous system increases, they show pleasant and exciting effects.
3. Dopamine (DA)DA is unevenly distributed in the brain. Most of DA is concentrated in striatum, substantia nigra and globus pallidus, and its receptors are D 1 and D2. There are ① substantia nigra-striatum pathways in the brain: they belong to the extrapyramidal system, which coordinate the movement. When the function of this pathway is weakened, it will cause Parkinson's disease and ADHD will appear. ② Midbrain-limbic system pathway: Function is related to mood and emotion. ③ Midbrain-cortex pathway: Function is related to spirit and reason. ④ Nodule-funnel pathway: responsible for endocrine function of anterior pituitary. The dysfunction of the second and third pathways in schizophrenia is accompanied by the increase of DA receptors in the brain. Antischizophrenia drugs work by blocking D2 receptors in these two pathways. Blocking substantia nigra-striatum and nodule-infundibulum pathways caused extrapyramidal side effects and endocrine changes respectively.
4. The content of 5- hydroxytryptamine (5-HT) is the highest in the central nervous system, and its receptors are divided into S 1 and S2 types. Its function is to maintain emotional stability and participate in the regulation of body temperature, sleep and endocrine. The main function of 5-HT is inhibition and stability, while the main function of NA is excitement and excitement.
5. GABA exists in the brain, mainly in substantia nigra and globus pallidus. GABA is a central inhibitory transmitter. For example, the lack of GABA in the cerebral cortex of epileptic patients can cause convulsions, and sodium valproate is effective for all kinds of epileptic seizures because it can inhibit the degradation of GABA.
6. Endoopioid peptides are referred to as endogenous opioid peptides, which are the contents of striatum, hypothalamus and pituitary in the brain. Opioids (mainly morphine) have sedative, hypnotic, antitussive and respiratory inhibitory effects.
7. Histamine (H) Histamine is unevenly distributed in the brain, and its content is high in hypothalamus and reticular structure. Receptors are divided into H 1 and H2 types. It has the effects of regulating mental activity, lowering body temperature, increasing water intake and causing vomiting. The excitement of H 1 receptor in the brain is stimulated, while the excitement of H2 receptor is inhibited. The drowsiness side effect of antihistamines may be related to blocking H 1 receptor.
8. Prostaglandin (PG)PG is evenly distributed in all regions of the brain. It is known that many PGs have thermal effect, and PGE2 has thermal effect. Central PG synthase (cyclooxygenase) inhibitors, such as acetylsalicylic acid, reduce PG synthesis and show antipyretic effect.
Second, the basic mode of drug action in the central nervous system
(1) directly acts on the receptor: excites or blocks the receptor.
(2) Affect the transmission process of transmitters: affect synthesis, storage, release, re-uptake, metabolism and inactivation.
(3) It affects the energy metabolism and membrane stability of nerve cells.
Three, the classification of central nervous system drugs
1, central stimulant.
2. Central depressants: general anesthetics, sedatives and hypnotics, antiepileptic drugs, anti-tremor and paralysis drugs, antipsychotics, analgesics, antipyretic and analgesic drugs.