pethidine

Action and Spectrum

Actions and spectrum: 

Action: pethidine acts as an agonist at opioid receptors in the central nervous system. It primarily interacts with the mu-opioid receptors, which are involved in pain perception, modulation, and response. By binding to these receptors, pethidine inhibits pain signals transmission and alters the perception of pain in the brain. 

Spectrum:  

• Acute Pain: pethidine is often used to provide relief from acute pain, such as postoperative pain, trauma-related pain, and pain associated with medical procedures. 
• Chronic Pain: In certain cases, pethidine may be prescribed for chronic pain management, such as in cancer patients or individuals with chronic painful conditions. 
• Labor Pain: pethidine is sometimes used during labor to help manage pain during childbirth. It provides pain relief and relaxation while allowing the individual to remain somewhat alert and responsive. 
• Anesthesia: pethidine can be used as an adjunct to anesthesia in some surgical procedures to manage pain during and after surgery. 

Drug Interaction

Adverse Reaction

Frequency not defined 

Adrenal insufficiency 

constipation 

Visual disturbances 

nausea 

Hypersensitivity reaction 

urticaria 

convulsions 

Headache 

Agitation 

Dizziness 

CNS depression 

severe hypotension 

Bradycardia 

Tachycardia 

Palpitation 

Hypogonadism 

Black Box Warning

Black Box Warning:  

pethidine carries a black box warning due to its potential for serious or fatal respiratory depression, especially when used in high doses, with certain medications, or in patients with respiratory conditions. The warning also highlights the risk of abuse, addiction, and neonatal withdrawal syndrome when used during pregnancy. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

• Respiratory Depression: pethidine is contraindicated in individuals who are already experiencing significant respiratory depression (slow and shallow breathing) or who have a history of respiratory depression. 
• Paralytic Ileus: pethidine should not be used in individuals with paralytic ileus, a condition characterized by a lack of bowel movements and intestinal blockage. 
• Hypersensitivity to Opioids: Individuals who have a known hypersensitivity or allergy to opioids, including pethidine, should not use the medication. 
• Severe Asthma: pethidine use is contraindicated in individuals with severe asthma or other respiratory conditions, as it can exacerbate respiratory depression and compromise breathing. 
• GI Obstruction: pethidine is contraindicated in individuals with gastrointestinal obstruction due to the risk of exacerbating the obstruction.

Caution: 

• Interactions with Other Medications: pethidine can interact with other medications, particularly central nervous system depressants, monoamine oxidase inhibitors (MAOIs), and serotonergic drugs. These interactions can lead to serotonin syndrome or enhance sedative effects. 
• Renal and Hepatic Impairment: pethidine is primarily metabolized by liver and excreted by kidneys. In impaired liver or kidney function, dosage adjustments may be necessary to prevent accumulation and potential toxicity. 
• Pregnancy and Lactation: pethidine crosses the placenta and can cause neonatal opioid withdrawal syndrome if used during pregnancy. Its use during labor and delivery is not recommended. pethidine can also be excreted in breast milk and may lead to sedation and respiratory depression in breastfeeding infants. 
• Individual Variation: Opioid sensitivity can vary among individuals. Patients should be monitored for efficacy, adverse effects, and signs of tolerance or withdrawal. 
• Avoid Abrupt Discontinuation: Abrupt discontinuation of pethidine after prolonged use can lead to withdrawal symptoms. Dosage should be tapered gradually under medical supervision.

Comorbidities: 

• Cardiovascular Conditions: pethidine can cause changes in heart rate and blood pressure. Patients with a history of cardiovascular diseases, such as heart failure or arrhythmias, should be closely monitored while taking pethidine. 
• Liver Dysfunction: pethidine is metabolized by the liver. Individuals with liver impairment or liver disease may experience altered drug metabolism, leading to higher levels of the medication in the bloodstream. Dose adjustments may be necessary in these cases. 
• Substance Use Disorder: Individuals with a history of substance abuse, including opioids, are at a higher risk of developing dependence on pethidine. Caution should be exercised, and alternative pain management options should be explored when possible. 
• Mental Health Conditions: pethidine’s effects on the central nervous system can interact with mental health conditions such as depression or anxiety. It may exacerbate symptoms or interact with medications used to manage these conditions. 
• Elderly and Frail Individuals: Elderly individuals or those who are frail may be more susceptible to the sedative effects of pethidine, increasing the risk of falls and other complications. 

Pregnancy / Lactation

Pregnancy consideration: Pregnancy Category: C 

Lactation: excreted into breast milk: unknown  

Pregnancy category: 

• Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester. 
• <b>Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 
• Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.   
• Category D: adequate data with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

pethidine, also known as meperidine, is a synthetic opioid analgesic medication with a mechanism of action like other opioids. It interacts with receptors in central nervous system to provide pain relief and alter the perception of pain. pethidine acts primarily as an agonist at the mu-opioid receptors, which are in brain, spinal cord, & peripheral tissues.

When it binds to these receptors, it inhibits the pain signals transmission and reduces the perception of pain. Additionally, pethidine has some affinity for the kappa-opioid receptors, which can contribute to its analgesic effects.  

Pharmacodynamics: 

Mu-Opioid Receptor Agonism: pethidine is an agonist of mu-opioid receptors in brain, spinal cord, and peripheral tissues. When pethidine binds to these receptors, it produces a series of effects, including: 

• Pain Relief: Activation of mu-opioid receptors reduces the pain signals transmission from peripheral nerves to brain. This modulation of pain perception leads to analgesia. 
• Euphoria and Sedation: Stimulation of mu-opioid receptors can induce feelings of euphoria, relaxation, and sedation. 
• Respiratory Depression: Activation of mu-opioid receptors in the brainstem can depress the respiratory centers, leading to slowed and shallow breathing. This effect is a significant concern with opioids. 

Kappa-Opioid Receptor Interaction: pethidine also has some affinity for kappa-opioid receptors. Activation of these receptors contributes to its analgesic effects, but it is thought to be less potent than its actions at the mu-opioid receptors. 

Histamine Release: pethidine can trigger histamine release from mast cells, leading to vasodilation, flushing, and itching. This histamine release can contribute to side effects like skin reactions and may be responsible for some of the differences in adverse effects compared to other opioids. 

Tolerance and Dependence: Long-term use of pethidine can lead to the development of tolerance, where the same dose becomes less effective over time, necessitating dose escalation for the same pain relief.  

Pharmacokinetics: 

Absorption 

pethidine is well-absorbed after oral administration, but its bioavailability can vary. It is also available in injectable forms for rapid onset of action. 

Distribution 

pethidine has a moderate distribution into tissues, including the brain, where it exerts its analgesic effects. It can cross placenta and enter breast milk. 

Metabolism 

pethidine is primarily metabolized in the liver by the enzyme cytochrome P450 2B6 to form normeperidine, its active metabolite. Normeperidine has a longer half-life than pethidine and can accumulate, leading to potential adverse effects. 

Elimination and excretion 

Both pethidine and normeperidine are excreted mainly in the urine. Kidney function plays an important role in the elimination of these compounds. 

Adminstartion

Administration: 

• Oral Tablets: pethidine is available in tablet form for oral administration. Tablets are typically taken with water and swallowed. The onset of action is slow when compared to intravenous administration. 
• Intramuscular (IM) Injection: pethidine can be administered as an intramuscular injection. This route is commonly used for quick pain relief in healthcare settings. The medication is injected into a muscle, often the thigh or upper arm. 
• Intravenous (IV) Injection: pethidine can be given as an intravenous injection directly into a vein. IV administration provides rapid onset of pain relief and is often used in emergency or surgical settings. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: pethidine 

Pronounced: (PEH-thuh-deen)  

Why do we use pethidine? 

• Postoperative Pain: pethidine is often used to manage pain after surgical procedures. It can help alleviate pain associated with surgical incisions, tissue trauma, and postoperative discomfort. 
• Labor Pain: pethidine is sometimes used during labor to provide pain relief for women experiencing childbirth. It can help reduce the intensity of contractions and provide comfort during labor. 
• Cancer Pain: pethidine may be used to manage cancer-related pain, particularly when other pain management strategies are insufficient. 
• Acute Pain: It is used for the relief of acute pain due to conditions such as kidney stones, pancreatitis, or other acute inflammatory conditions.