What Is a Topical Analgesic?

Analgesics are drugs that are mainly used in the central or peripheral nervous system to selectively suppress and relieve all kinds of pain, and to relieve pain and cause fear, tension, and anxiety. Including narcotic analgesics represented by morphine and antipyretic, analgesic and anti-inflammatory medicines represented by aspirin, they have played a huge role in relieving patients' pain. However, some analgesics are repeatedly used and prone to addiction. Drugs that are easily addictive, commonly known as "narcotic analgesics", are listed as "narcotic drugs" in drug administration. The state has promulgated the "Regulations on the Management of Narcotic Drugs", which strictly controls and restricts the production and supply of drugs. Protect people's health.

Drug Name: Analgesics
Whether prescription drugs: prescription
Main medication contraindications: Addictive

Athletes use with caution: Use with caution
Features: Reduce pain
Pharmacological action: Acts on the nervous system and causes nerve paralysis

Analgesics

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Analgesic pain definition

Pain is a protective response to the body following noxious stimuli, often accompanied by fear and tension

Analgesics , Restlessness and other emotional activities. Pain is another symptom of certain diseases, which can make people feel pain. In addition to severe pain reflected in sensory pain and emotional anxiety, it can lead to physiological disorders, insomnia, and even shock and life-threatening. Therefore, the appropriate use of analgesics in clinical practice to relieve severe pain and prevent shock is necessary, and it 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 the disease, so analgesics should not be easily used before the disease is diagnosed, so as not to cover up the disease and delay the diagnosis and treatment of the disease.

1 Analgesics1 Narcotic Analgesics

Principle of pharmacodynamics

Regarding the site of action of analgesics, the author of the Chinese Academy of Pharmaceutical Sciences in 1962 injected a small amount of morphine into the gray matter surrounding the third ventricle and the aqueduct of the rabbit. Inside the gray matter around the aqueduct. Subsequently, morphine receptors were discovered, and two enkephalins (methionine enkephalin and leucine enkephalin) were isolated from the brain. Their distribution in the brain was basically the same as that of morphine receptors. Several peptides are isolated from the pituitary gland, called endorphin. Endorphins have a similar effect to enkephalins. Collectively referred to as morphine-like substances.

Regarding the principle of analgesics, there are data that morphine-receptive ribbons and endorphinergic neurons exist in the center, and through the information transmission of morphine-like substances, the two are linked to form the "anti-pain system" in the body. It maintains the normal pain threshold and makes physiological anti-pain function. Analgesics such as morphine may act as agonists of the morphine receptor. By activating this receptor, it can increase the function of the anti-pain system in the brain, increase the pain threshold, and reduce the body's sensitivity to internal and external environmental stimuli. Analgesic effect.

Clinically used narcotic analgesics mainly include opioid alkaloids and synthetic analgesics.

Classification of analgesics

Analgesic receptor agonist

Narcotic analgesics are drugs that act on the central nervous system to relieve or reduce pain and change the emotional response to pain. Since these early drugs were natural opioid alkaloids or their semi-synthetic derivatives, narcotic analgesics are also known as opioid analgesics. Among them, fentanyl, morphine, and codeine are opioid receptor agonists, and pethidine is an artificial opioid receptor agonist.

Fentanyl injection has strong analgesic power, weak addiction, and short maintenance time. It is suitable for all stages of anesthesia and analgesia. It is also an anesthetic adjuvant in surgery. Fentanyl transdermal patches are convenient to administer, maintain blood concentration, reduce peak-valley effects, and have fewer adverse reactions.
Morphine is the preferred analgesic recommended by WHO. It is the third step of the "three-step analgesic treatment principle for cancer." It is the first 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 that country. Injection is mainly used for postoperative self-controlled analgesia (PCA); oral morphine controlled-release tablets are convenient to use, maintain stable blood concentration levels, have few adverse reactions, and have weak addiction. However, morphine has some adverse reactions such as nausea, vomiting, constipation, etc., and can cause respiratory depression, so it should be used with caution.

Pharmacological action

CNS system: (1) Analgesic and sedation: effective for a variety of pains (effects on dull pain> sharp pain), improving the emotional response to anxiety, tension and fear caused by pain, and accompanied by euphoria (2) Antitussive: directly suppress the cough center, reduce or disappear cough reflex, and produce antitussive effect. (3) Inhibition of breathing: A therapeutic amount of morphine can reduce the sensitivity of the respiratory center to CO2 tension in the blood and inhibit the pontine respiration adjustment center, slowing the breathing rate and reducing the tidal volume. (4) Reduction of pupils: parasympathetic nerves that dominate the pupils. Pupils shrink during poisoning, and needle-like pupils are characteristic of poisoning. (5) Others: Nausea and vomiting caused by CTZ. Inhibit hypothalamic release of gonadotropin-releasing hormone, corticotropin-releasing hormone, etc.

Smooth muscle: (1) Gastrointestinal smooth muscle: morphine reduces gastrointestinal motility, increases gastrointestinal tension, and easily causes constipation. (2) Biliary smooth muscle: A therapeutic amount of morphine causes spasmodic contraction of the biliary audi sphincter, which can cause biliary colic. Atropine can be partially relieved. (3) Other smooth muscles: Reduced uterine tension of morphine can prolong the delivery time of women; increase tension of ureteral smooth muscles and bladder sphincter can cause urinary retention; large doses can cause bronchoconstriction, induce or worsen asthma.

Cardiovascular system: (1) can dilate blood vessels, reduce peripheral resistance, and orthostatic hypotension can occur. (2) Inhibit breathing to accumulate CO2 in the body, indirectly dilate cerebral blood vessels and increase intracranial pressure. (3) It has protective effect on myocardial ischemic injury.

Others: Suppress the immune system and the immune response induced by HIV proteins.

Mechanism

Analgesic mechanism: During the transmission of pain to the center, pain stimulates the sensory nerve endings and releases Glu and SP, which acts on the corresponding receptors to complete the transfer of pain urges to the center and cause pain. Endogenous opioid peptides can stimulate the opioid receptors on the presynaptic and posterior membranes of sensory neurons when released by specific neurons. Through the G-protein coupling mechanism, they inhibit adenylate cyclase, promote K ⁺ outflow, and reduce Ca ²⁺ influx reduces the release of presynaptic membrane transmitters, hyperpolarizes the postsynaptic membrane, and ultimately weakens or blocks the transmission of pain signals, which produces analgesic effects.

Morphine stimulates the gray matter receptors in the spinal cord glia, medial thalamus, ventricle, and aqueduct to mimic endogenous opioid peptides and exert analgesic effects. Acting on opioid receptors in the limbic system and blue spots, it can slow down Unpleasant and anxious emotions and euphoria caused by pain.

Clinical application

(1) Analgesia: Used for pain of various causes, but only for short-term application when cancer pain and other analgesics are ineffective. Relieves acute pain caused by myocardial infarction. Features: strong effect, central analgesic effect, addictive. (2) Adjuvant treatment of cardiogenic asthma: It is pulmonary edema caused by acute left heart failure and requires comprehensive treatment. In addition to strengthening the heart, diuresis, and oxygen, intravenous morphine can produce good results. Treatment mechanism: 1) morphine dilates blood vessels, reduces blood volume and reduces heart burden; 2) sedative effect, eliminates patients' anxiety and fear; 3) suppresses breathing, reduces the sensitivity of the respiratory center to carbon dioxide, and makes the breathing change from shallow to deep . (3) Antidiarrheal: Opioids can be used to treat simple diarrhea.

Adverse reactions

Treatment amount: nausea, vomiting, constipation, dysuria, etc.

Tolerance and dependence: The former refers to the decrease in the sensitivity of the central nervous system to it after long-term use, and the dose needs to be increased to achieve the original efficacy. The latter refers to the characteristics of this class of drugs that are repeatedly used by users, and they can be divided into physical dependence and psychological dependence.

Acute poisoning: manifestation of coma, extremely dilated pupils, deep respiratory depression, decreased blood pressure, severe hypoxia, and urinary retention, etc., mostly due to respiratory paralysis. Rescue: artificial respiration, appropriate oxygen, intravenous naloxone.

Partial analgesic receptor

Opioid receptor partial agonist

Common characteristics: Most have partial agonist characteristics. Some drugs are agonists for certain receptor subtypes and antagonists for other subtypes, also known as opioid receptor mixed agonist / antagonist. It is mainly analgesic, with less dependence and weak respiratory depression, but causes mental symptoms such as anxiety and hallucinations.

Pentazocine (pentazocine)

It stimulates receptors and blocks receptors, and its analgesic intensity is 1/3 of morphine.

No narcotic drugs (less addictive) are included, but they are still in the category of "psychotropic drugs".

Increasing the dose can cause irritability, hallucinations, nightmares, increased blood pressure, increased heart rate (associated with increasing plasma NA levels), mental disturbances and dysphonia.

It is used for a variety of chronic pains, not for pain during myocardial infarction.

Butorphanol

Activates kappa receptors; weakly blocks mu receptors.

Analgesic effect and respiratory depression: 3.5-7 times of morphine. Increase vascular resistance and increase heart work.

It is used for moderate and severe pain and has better effect on acute pain than chronic pain.

Opioid receptor antagonist

Naloxone

Competitive antagonistic effect on all types of opioid receptors: > >

Treatment of opioid overdose: rescue respiratory depression and central depression. Diagnose drug addiction: can induce withdrawal symptoms. Treatment of toxic shock from alcoholism and infection. Experimental research tool medicine.

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 were no obvious side effects such as constipation, urinary retention and orthostatic hypotension, and euphoria and addiction were lower than morphine.

Pethidine

Pharmacological action

Analgesia and sedation (with analgesic intensity of 1/10 to 1/7 of morphine); sedative, respiratory depression, euphoric and vasodilator effects are comparable to morphine; does not cause constipation and urinary retention; does not prolong labor; large doses may Causes bronchial smooth muscle contraction.

Clinical application

Analgesia: used in place of morphine for all kinds of severe pain (trauma, postoperative, cancer), visceral colic (combined with antispasmodics), and labor pain (not used 2 to 4 hours before delivery).

Cardiogenic asthma.

Dosing before anesthesia.

Artificial hibernation (combined with chlorpromazine and promethazine).

^[1] (methadone)

Compared with morphine, methadone has the same analgesic intensity, longer duration, weaker sedation, slower tolerance and addiction, and milder withdrawal symptoms.

Morphine injection after oral methadone can not cause the original euphoria, nor does it show withdrawal symptoms, thus weakening the addiction of morphine and so on.

It is suitable for the detoxification of severe pain caused by trauma, surgery and advanced cancer, morphine, heroin and other addictions.

Fentanyl and its homologs

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

Sufentanil and alfentanil are both analogs of fentanyl. Sufentanil has a stronger analgesic effect than fentanyl, 1000 times that of morphine, and alfentanil is weaker than fentanyl. The two drugs have little effect on the cardiovascular system and are often used for cardiovascular anesthesia.

Dihydroetorphine

Strong analgesics produced for our country, its analgesic effect is 500 to 1000 times that of morphine. This product excites the m receptor and has a weak effect on the d and k receptors.

Clinically used in pethidine, morphine and other ineffective chronic refractory pain and advanced cancer pain.

Tramadol

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 were weak. No significant cardiovascular effect.

For moderate to severe acute and chronic pain.

Rotundine

The active part is the L-body of fumaricin.

Has sedative, stable, analgesic and central muscle relaxation effects. May be related to promoting the synthesis and release of enkephalin and endorphin, blocking DA receptors in the brain.

Good effect on chronic persistent dull pain. It is used for gastrointestinal system dull pain, general headache, headache after concussion, and has less effect on traumatic and cancerous pain. ^[2]

2 Analgesics 2 Antipyretics and Analgesics

Antipyretic and analgesic anti-inflammatory drugs are a class of drugs with antipyretic and analgesic effects. The analgesic effect of this class of drugs is mainly in the periphery. When the tissue is damaged or inflamed, PG, bradykinin, histamine, 5-HT and other painful substances are locally produced and released to cause pain. Can significantly increase the sensitivity of pain sensory nerve endings to pain-promoting substances such as bradykinin, and produce persistent dull pain. NSAIDs can inhibit PG synthesis during inflammation, and thus have a good analgesic effect on chronic dull pain. Includes salicylic acid (aspirin), aniline (acetaminophen), pyrazolone, indoleacetic acid, acetic acid, 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 the treatment of chronic pain. Small doses have anti-platelet aggregation effect. Can prolong bleeding time and inhibit the formation of cardio-cerebral thrombosis.
2.2 Paracetamol Paracetamol has a strong antipyretic effect, mainly because the drug has a strong inhibitory effect on prostaglandin synthesis in the central nervous system, and has a similar effect with aspirin, and its analgesic effect is relatively weak, but Long-lasting and soothing effect. There is almost no anti-rheumatic, anti-inflammatory effect. This product has less irritation to the gastrointestinal tract, does not affect the coagulation mechanism, and does not affect liver function at normal doses. It is a safe and effective antipyretic analgesic with a low incidence of adverse reactions. Preferred antipyretic.
2.3 Diclofenac Diclofenac is a non-steroidal anti-inflammatory drug with good oral absorption and an anti-inflammatory effect that is 26-50 times higher than aspirin. It can better improve symptoms such as swelling and joint pain, and it can also enhance activity Especially good at treating joint diseases in the elderly. However, adverse effects such as bone marrow suppression may occur when taking this product, so when used as a prescription drug, it is limited to external use.
2.4 Ibuprofen Ibuprofen is relatively easy to absorb by mouth, and the side effects of the drug are relatively small. It has anti-inflammatory, anti-rheumatic, antipyretic and analgesic effects. Compared with aspirin, its analgesic effect is about 20 times higher; The anti-inflammatory effect of ibuprofen is average, and the antipyretic effect is obvious and long-lasting.
2.5 Indomethacin Indomethacin has a very strong analgesic effect. The analgesic effect is particularly obvious when treating inflammatory pain. Its analgesic intensity is equivalent to 10 times to 12 times of the same dose of aspirin; the effect is the best. However, due to its many adverse reactions, it is limited to external use when 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 is combined with plasma proteins. The drug half-life is 13-14 hours. About 95% are excreted from the urine as metabolites or prototypes. It has a significant effect on osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, chronic diseases of the motor system, and gout, mild and moderate pain. 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, because of its side effects, breastfeeding women and children under 2 years of age should be disabled.

2.7 Nimesulide Nimesulide is a non-steroidal anti-inflammatory drug with obvious analgesic, anti-inflammatory and antipyretic effects. It is particularly good at treating various chronic pains, such as osteoarthritis, trauma, headache, rheumatism , Cancer pain, etc. At the same time, the drug has small side effects, so it is widely used in clinical practice, especially in the selection of antipyretic analgesics in children, it is even recognized by doctors and parents. However, this product, like other non-steroidal anti-inflammatory drugs, may produce adverse drug reactions. The most common are drowsiness, dizziness, gastrointestinal bleeding, or gastric ulcers. Pediatric experts also clearly point out that children should use nimesulide with caution The most common adverse reaction of the drug in children is leukopenia, so the National Adverse Drug Reaction Monitoring Center has been paying attention to the clinical use of nimesulide and continuously monitoring relevant test data at home and abroad. About nimesulide Experts need to further demonstrate the related risk issues. ^[3]