Analgesics: Uses, Types, And Precautions

Analgesics mainly act on the central or peripheral nervous system, selectively inhibiting and relieving various pains, and alleviating pain and causing fear of nervousness and restless mood and pain.

Including anesthetic analgesics represented by morphine and antipyretic analgesic and anti-inflammatory drugs represented by aspirin have played a huge role in relieving the suffering of patients.
Emotional activities such as uneasiness. Pain is a symptom of certain diseases that can cause pain. Severe pain is reflected in sensory pain and emotional uneasiness, and can lead to physiological dysfunction, causing insomnia, andeven shock and life-threatening.

Therefore, the appropriate use of analgesics in clinical practice to relieve severe pain and prevent shock is necessary, and is of great significance in the treatment of diseases and trauma care.
On the other hand, the location and nature of pain is an important basis for diagnosing diseases. Therefore, it is not advisable to use analgesics easily before the disease is diagnosed, so as not to cover up the disease and delay the diagnosis and treatment of the disease.

Pain definition

Pain is a protective reaction that occurs when the body is subjected to noxious stimulation, often accompanied by fear and tension.

Principle of pharmacodynamics

Regarding the action site of analgesics, Chinese pharmacological workers injected trace morphine into the gray matter around the third ventricle and the aqueduct in rabbits in 1962, and found significant analgesic effect.

Firstly, the morphine action site was mainly in the third ventricle and Inside the gray matter around the water conduit. Following the discovery of morphine receptors, two enkephalins (methionine enkephalin and leucine enkephalin) were isolated from the brain and their distribution in the brain was essentially consistent with the morphine receptor.

Several peptides, called endorphins, were isolated from the pituitary. Endorphins have an action similar to enkephalin. It is collectively referred to as a morphine-like substance.

Regarding the principle of analgesics, there is information that the central morphine is affected by the ribbon and the endorphin neuron, through the information transfer of morphine-like substances, and the two are linked together to form an “anti-pain system” in the body.

Maintain a normal pain threshold and make physiological anti-pain function. Analgesics such as morphine may act as agonists of morphine receptors, stimulating the receptor, increasing the function of the anti-pain system in the brain through various links, increasing the pain threshold, and weakening the susceptibility of the body to internal and external environmental stimuli.

Classification

Receptor agonist

An anesthetic analgesic is a drug that acts on the central nervous system to relieve or relieve pain and alter the emotional response to pain.

Since these early drugs are natural opioid alkaloids or semi-synthetic derivatives, narcotic analgesics are also known as opioid analgesics. Among them, fentanyl, morphine and codeine are opioid receptor agonists, and meperidine is a synthetic opioid receptor agonist.

Fentanyl injection has strong analgesic ability, weak addiction and short maintenance time. It is suitable for all phases of anesthesia and analgesia. It is also an anesthetic adjuvant in surgery. The fentanyl transdermal patch is convenient for administration, maintains blood concentration, reduces peak-to-valley effect, and has few adverse reactions.

Morphine is the recommended analgesic recommended by WHO and the third step in the “Three-step pain treatment principle for cancer”.

It is the drug of choice for severe cancer pain. WHO experts believe that morphine consumption in a country is an important indicator of the improvement in cancer pain in the country.

The injection is mainly used for postoperative controlled analgesia (PCA); oral morphine controlled release tablets are convenient to use, the blood drug concentration level is stable, and the adverse reactions are less, and the addiction is weak.

However, morphine has some adverse reactions such as nausea, vomiting, constipation, etc., and can also cause respiratory depression, so it should be used with caution.

Pharmacological action

CNS system

(1) analgesic sedation: effective for a variety of pain (effect on dull pain > sharp pain), improve anxiety, nervousness, fear and other emotional reactions caused by pain, and may be accompanied by euphoria.

(2) Antitussive: directly inhibits the cough center, so that the cough reflex is reduced or disappeared, thereby producing an antitussive effect.

(3) Respiratory inhibition: The therapeutic amount of morphine can reduce the sensitivity of the respiratory center to blood CO2 tension and inhibit the pons respiration adjustment center, so that the respiratory rate is slowed down and the tidal volume is reduced.

(4) Degeneration: Excited parasympathetic nerves that control the pupil. When the poisoning is reduced, the pupil is narrowed, and the needle-like pupil is a poisonous feature.

(5) Others: Excited cerebral CTZ caused nausea and vomiting. It inhibits the release of gonadotropin-releasing hormone and corticotropin-releasing hormone from the hypothalamus.

Smooth muscle

(1) gastrointestinal smooth muscle: morphine reduces gastrointestinal motility, increases gastrointestinal tension, and easily causes constipation.

(2) biliary smooth muscle: the therapeutic amount of morphine causes biliary tract sphincter spasm contraction, which can cause biliary colic. Atropine can be partially relieved.

(3) other smooth muscle: morphine reduces uterine tension can prolong the maternal delivery time; improve ureteral smooth muscle and bladder sphincter tension, can cause urinary retention; large doses can cause bronchoconstriction, induce or aggravate asthma.

Cardiovascular system

(1) can expand blood vessels, reduce peripheral resistance, and can develop orthostatic hypotension.

(2) Inhibition of breathing causes CO2 accumulation in the body, indirectly dilating the cerebral blood vessels and increasing intracranial pressure.

(3) It has a protective effect on myocardial ischemic injury.

Other: inhibits the immune system and HIV protein-induced immune response.

Mechanism

Analgesia mechanism: During the transmission of pain sensation to the central nervous system, pain sensation stimulates the sensory nerve endings and releases Glu and SP, acting on the corresponding receptors to complete the transmission of painful impulses to the central center and causing pain.

Endogenous opioid peptides are evoked by specific neurons and can evoke opioid receptors in the presynaptic and posterior membranes of the sensory synapses, inhibit adenylate cyclase, promote K+ efflux, and reduce Ca2+ through G-protein coupling mechanism.
I

nflow causes a decrease in presynaptic membrane transmitter release, hyperpolarization of the postsynaptic membrane, and ultimately attenuates or blocks the transmission of pain signals, resulting in an analgesic effect.

Morphine drugs exert an analgesic effect by stimulating endogenous opioid peptides in the glial zone of the spinal cord, the medial thalamus, the ventricles, and the periplasmic gray receptors around the aqueduct, acting on the limbic system and the opioid receptors of the blue spot. Unpleasant, anxious and other emotions caused by pain and euphoria.

Clinical application

Analgesia: Pain for various reasons, but only for short-term use when cancer pain and other analgesics are ineffective. Relieve severe pain caused by myocardial infarction. Features: strong, central analgesic effect, addictive.

Cardiac asthma adjuvant therapy: pulmonary edema caused by acute left heart failure, comprehensive treatment is required. In addition to cardiac, diuretic, and oxygen, intravenous morphine can produce good results.
Adverse reactions

The amount of treatment: nausea, vomiting, constipation, difficulty urinating, etc.

Tolerance and dependence: The former refers to the reduction of sensitivity of the central nervous system after long-term use, and it is necessary to increase the dose to achieve the original efficacy.

The latter refers to the characteristics of the drugs that users will add to after being repeatedly used by people, and can be divided into physical dependence and psychological dependence.

Acute poisoning: manifested as coma, extreme dilated pupils, deep respiratory depression, decreased blood pressure, severe hypoxia, and urinary retention, and more than respiratory paralysis. Rescue: artificial respiration, moderate oxygen, intravenous naloxone.

Partial excitatory receptor

Opioid receptor partial agonist

Common features: Most have partial agonist characteristics. Some drugs are agonists for certain receptor subtypes and antagonists for other subtypes, also known as mixed agonists/antagonists.

It is mainly analgesic, with less dependence and weaker respiratory inhibition, but causes mental symptoms such as anxiety and hallucinations.

Pentazone (pentazocine, analgesic new)

The κ receptor is agonized and the μ receptor is blocked, and the analgesic intensity is 1/3 of that of morphine.

Narcotic drugs are not included (small addiction), but they are still in the scope of “psychotic drugs”.
Increased doses can cause irritability, hallucinations, nightmares, elevated blood pressure, increased heart rate (related to increased plasma levels of NA), thinking disorders, and difficulty in pronunciation.
It is used for a variety of chronic pain and is not suitable for pain in myocardial infarction.

Butorphanol

Agonated kappa receptor; weakly blocked μ receptor.
Analgesic efficacy and respiratory inhibition: 3.5 to 7 times that of morphine. Increase vascular resistance and increase heart work.
For moderate to severe pain, it is better for acute pain than for chronic pain.

Naloxone

Competitive antagonism for various opioid receptors: μ>κ>δ
Treatment of opioid overdose: rescue of respiratory depression and central inhibition. Diagnosis of drug addiction: can induce withdrawal symptoms. Alcoholism, treatment of toxic shock. Experimental research tools.

Other analgesics

Codeine

The effect is similar to morphine, but the intensity is weak. The analgesic effect is about 1/10 of morphine. The antitussive effect is about 1/4 of morphine. For moderate pain and severe dry cough. There are no obvious side effects such as constipation, urinary retention and orthostatic hypotension, and euphoria and addiction are also lower than morphine

Pharmacological action

Analgesia, sedation (analgesia is 1/10 to 1/7 of morphine); sedation, respiratory depression, euphoria and vasodilation are comparable to morphine; do not cause constipation and urinary retention; do not prolong labor; large doses Causes bronchial smooth muscle contraction.

Artificial hibernation (combined with chlorpromazine, promethazine).

Methadone

Compared with morphine, methadone has the same analgesic effect, longer duration, less sedative effect, slower tolerance and addiction, and slightly less withdrawal symptoms.

The injection of morphine after oral methadone does not cause the original euphoria, and there is no withdrawal symptoms, thus reducing the addictiveness of morphine and the like.

It is suitable for the treatment of trauma, surgery and advanced cancer, such as severe pain, morphine, heroin and other addiction treatments.

Fentanyl and its homologs

Short-acting analgesics (100 times the intensity of morphine), used for anesthesia and intravenous anesthesia, or combined with droperidol to produce nerve block analgesia.

Both sufentanil and alfentanil are analogs of fentanyl. The analgesic effect of sufentanil is stronger than that of fentanyl, which is 1000 times that of morphine, while alfentanil is weaker than fentanyl. The two drugs have little effect on the cardiovascular system and are often used for cardiovascular surgery anesthesia.

Dihydroetorphine

The analgesic effect of the strong analgesics produced in China is 500 to 1000 times that of morphine. This product is excited by m receptor and has weak effect on d and k receptors.
Clinically used for ineffective chronic intractable pain and advanced cancer pain such as meperidine or morphine.

Tramadol

μ receptor weak agonist, NA, 5-HT reuptake inhibitor.
The analgesic effect is similar to pentazocine. The antitussive effect is half that of codeine. Respiratory depression,

smooth muscle spasm, and dependence are weak. No significant cardiovascular effects.
Suitable for moderate and severe acute and chronic pain.

Rotundine

The effective part is the left-handed body of tetrahydropalmatine.
It has calming, stability, analgesia and central muscle relaxation. It may be related to promoting the synthesis and release of enkephalin and endorphin and blocking the DA receptor in the brain.

It has a good effect on chronic persistent dull pain. For gastrointestinal system dull pain, general headache, headache after concussion, poor effect on traumatic and cancerous pain.

Antipyretic analgesics

Antipyretic analgesic and anti-inflammatory drugs are a class of drugs with antipyretic and analgesic effects. The analgesic action site of this class of drugs is mainly in the periphery.

When the tissue is damaged or inflamed, local production and release of PG, bradykinin, histamine, 5-HT and other pain-causing substances cause pain, and PG not only has its own pain, and It can significantly improve the sensitivity of pain nerve endings to pain-causing substances such as bradykinin, resulting in persistent dull pain. NSAIDs inhibit P G synthesis during inflammation and thus have a good analgesic effect on chronic dull pain. These include salicylic acid (aspirin), aniline (acetaminophen), pyrazolone, indole acetic acid, acid-killing, propionic acid and oxicam. The main drugs are as follows:

2.1 Aspirin

Aspirin has strong anti-rheumatic, anti-inflammatory, antipyretic and analgesic effects, and has achieved good results in treating chronic pain. Small doses have anti-platelet aggregation. It can prolong the bleeding time and inhibit the formation of heart and brain thrombosis.

2.2 Acetaminophen

Acetaminophen has a strong antipyretic effect, mainly because the drug has a strong inhibitory effect on the synthesis of prostaglandins in the central nervous system, and has similar effects as aspirin. The analgesic effect is relatively weak, but the effect is long-lasting and moderate.

There is almost no anti-rheumatic and anti-inflammatory effect. This product is less irritating to the gastrointestinal tract, does not affect the blood coagulation mechanism, does not affect liver function under normal dose, is a safe and effective antipyretic analgesic, and has a low incidence of adverse reactions, which is recommended by the World Health Organization. The preferred antipyretic.

2.3 Diclofenac

Diclofenac is a non-steroidal anti-inflammatory drug with good oral absorption, anti-inflammatory effect 26-40 times higher than aspirin, can better improve swelling, joint pain and other symptoms, but also has the function of enhancing activities, especially good at Treatment of senile joint disease. However, taking this product may cause adverse drug effects such as myelosuppression, so it is only for external use when used as a prescription drug.

2.4 Ibuprofen

Ibuprofen is relatively easy to absorb orally, has relatively small side effects, and has anti-inflammatory, anti-rheumatic, antipyretic and analgesic effects. Its analgesic effect is about 20 times higher than that of aspirin; ibuprofen The anti-inflammatory effect is general, and the antipyretic effect is obvious and lasting.

2.5 Indomethacin

Indomethacin has a strong analgesic effect. The analgesic effect is particularly obvious when treating inflammatory pain. The analgesic intensity is equivalent to 10 times to 12 times that of the same dose of aspirin; the effect is best. However, since it has many adverse reactions, it is only used for external use when it is used as an over-the-counter drug.

2.6 naproxen

Naproxen is a non-steroidal anti-inflammatory drug with antipyretic, anti-inflammatory and analgesic effects. The oral absorption is good and the effect is fast. The plasma concentration reaches a peak after 2-4 hours after administration, and most of the blood binds to plasma protein, and the drug half-life is 13-14h. About 95% are excreted from the urine as metabolites or protoplasts.

For osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, chronic diseases of the motor system, gout, mild to moderate pain, etc., have a significant effect. Moderate pain can be relieved after taking the drug for 1 hour, and the analgesic effect can be maintained for more than 7 hours. However, lactating women and children under 2 years of age should be banned because of their side effects.

2.7 Nimesul

Nimesulide is a non-steroidal anti-inflammatory drug with obvious analgesic, anti-inflammatory and antipyretic effects. It is especially good at treating various chronic pain treatments, such as bone and joint inflammation, traumatic pain, headache, rheumatic pain, cancer pain, etc.

At the same time, the drug has less side effects and is widely used in the clinic, especially in the selection and administration of antipyretic analgesics in children. However, this product, like other non-steroidal anti-inflammatory drugs, may cause adverse drug reactions.

The most common ones are lethargy, dizziness, gastrointestinal bleeding or gastric ulcer. Pediatric experts also clearly point out that children should be careful with nimesulide. The most common adverse reaction of this drug in children’s medication is leukopenia.

Therefore, the National Center for Adverse Drug Reaction Monitoring has been paying attention to the clinical use of nimesulide and constantly monitoring the relevant test data at home and abroad. The relevant risks issue, experts need further argumentation. [3]